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Background: A definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022. Methods: The study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: (A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); (B) Lymphocyte B, CD4 and CD8 T-cell phenotype; (C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender. Result: We studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VACno), whilst 63% had received 2 (VAC2) or 3 doses (VAC3) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC3 vs. 43% in VAC2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S (p = 0.0060), B (p = 0.0079), CD8 (p = 0.0043) and Th2 cell counts (p = 0.0131) were higher in VAC2 + 3 compared to VACno. Delta variant was the most representative in VAC2 (n = 13/18, 72%), detected in 41% of VACno, whereas undetected in VAC3, and anti-RBD-S production was higher in VAC2 vs. VACno (p = 0.0001), alongside neutralization against Delta (p = 0141), BA1 (p = 0.0255), BA4/5 (p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010). Conclusions: Administration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitude of the humoral response against the original SARS-CoV-2 and emerging variants. A systematic surveillance of the emerging variants is paramount to define future vaccination strategies. [ABSTRACT FROM AUTHOR]

Abstract Background A definition of the immunological features of COVID-19 pneumonia is needed to support clinical management of aged patients. In this study, we characterized the humoral and cellular immune responses in presence or absence of SARS-CoV-2 vaccination, in aged patients admitted to the IRCCS San Raffaele Hospital (Italy) for COVID-19 pneumonia between November 2021 and March 2022. Methods The study was approved by local authorities. Disease severity was evaluated according to WHO guidelines. We tested: (A) anti-SARS-CoV-2 humoral response (anti-RBD-S IgG, anti-S IgM, anti-N IgG, neutralizing activity against Delta, BA1, BA4/5 variants); (B) Lymphocyte B, CD4 and CD8 T-cell phenotype; (C) plasma cytokines. The impact of vaccine administration and different variants on the immunological responses was evaluated using standard linear regression models and Tobit models for censored outcomes adjusted for age, vaccine doses and gender. Result We studied 47 aged patients (median age 78.41), 22 (47%) female, 33 (70%) older than 70 years (elderly). At hospital admission, 36% were unvaccinated (VACno), whilst 63% had received 2 (VAC2) or 3 doses (VAC3) of vaccine. During hospitalization, WHO score > 5 was higher in unvaccinated (14% in VAC3 vs. 43% in VAC2 and 44% VACno). Independently from vaccination doses and gender, elderly had overall reduced anti-SARS-CoV-2 humoral response (IgG-RBD-S, p = 0.0075). By linear regression, the anti-RBD-S (p = 0.0060), B (p = 0.0079), CD8 (p = 0.0043) and Th2 cell counts (p = 0.0131) were higher in VAC2 + 3 compared to VACno. Delta variant was the most representative in VAC2 (n = 13/18, 72%), detected in 41% of VACno, whereas undetected in VAC3, and anti-RBD-S production was higher in VAC2 vs. VACno (p = 0.0001), alongside neutralization against Delta (p = 0141), BA1 (p = 0.0255), BA4/5 (p = 0.0162). Infections with Delta also drove an increase of pro-inflammatory cytokines (IFN-α, p = 0.0463; IL-6, p = 0.0010). Conclusions Administration of 3 vaccination doses reduces the severe symptomatology in aged and elderly. Vaccination showed a strong association with anti-SARS-CoV-2 humoral response and an expansion of Th2 T-cells populations, independently of age. Delta variants and number of vaccine doses affected the magnitude of the humoral response against the original SARS-CoV-2 and emerging variants. A systematic surveillance of the emerging variants is paramount to define future vaccination strategies.

Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the “positive effect” and “no effect” groups, except for IL20, which was 2.61 times higher in the “positive effect” group compared to the “no effect” group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the “positive effect” group. The increase in ICAM1 in the “no effect” group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.

The 2017 World Health Organization Fact Sheet highlights that coronary artery disease is the leading cause of death globally, responsible for approximately 30% of all deaths. In this context, machine learning (ML) technology is crucial in identifying coronary artery disease, thereby saving lives. ML algorithms can potentially analyze complex patterns and correlations within medical data, enabling early detection and accurate diagnosis of CAD. By leveraging ML technology, healthcare professionals can make informed decisions and implement timely interventions, ultimately leading to improved outcomes and potentially reducing the mortality rate associated with coronary artery disease. Machine learning algorithms create non-invasive, quick, accurate, and economical diagnoses. As a result, machine learning algorithms can be employed to supplement existing approaches or as a forerunner to them. This study shows how to use the CNN classifier and RNN based on the LSTM classifier in deep learning to attain targeted “risk” CAD categorization utilizing an evolving set of 450 cytokine biomarkers that could be used as suggestive solid predictive variables for treatment. The two used classifiers are based on these “45” different cytokine prediction characteristics. The best Area Under the Receiver Operating Characteristic curve (AUROC) score achieved is (0.98) for a confidence interval (CI) of 95; the classifier RNN-LSTM used “450” cytokine biomarkers had a great (AUROC) score of 0.99 with a confidence interval of 0.95 the percentage 95, the CNN model containing cytokines received the second best AUROC score (0.92). The RNN-LSTM classifier considerably beats the CNN classifier regarding AUROC scores, as evidenced by a p-value smaller than 7.48 obtained via an independent t-test. As large-scale initiatives to achieve early, rapid, reliable, inexpensive, and accessible individual identification of CAD risk gain traction, robust machine learning algorithms can now augment older methods such as angiography. Incorporating 65 new sensitive cytokine biomarkers can increase early detection even more. Investigating the novel involvement of cytokines in CAD could lead to better risk detection, disease mechanism discovery, and new therapy options.

Background: Mycobacterium (M.) tuberculosis-caused immunopathology is characterized by aberrant expression of plasma cytokines in human tuberculosis. Disease severity and long-term anti-mycobacterial treatment are potentially influenced by immunopathology and normalization of plasma cytokine levels during therapy may indicate treatment efficacy and recovery. Study design and methods: In this study, we analyzed the concentrations of selected plasma cytokines (i.e., IL-6, IP-10, IL-10, IL-22, IFNγ, GM-CSF, IL-8) and M. tuberculosis sputum burden in patients with tuberculosis (n = 76). Cytokine levels were compared to healthy contacts (n = 40) and changes under treatment were monitored (i.e., 6 and 16 weeks after treatment start). According to differences in M. tuberculosis sputum burden and conversion, tuberculosis patients were classified as paucibacillary as well as 'rapid' or 'slow' treatment responders. A subgroup of tuberculosis patients had fatal disease courses. Results: Six of seven cytokines were significantly higher in tuberculosis patients as compared to contacts and four of these (i.e., IL-6, IP-10, IL-10, and IL-22) were detectable in the majority of tuberculosis patients. IL-6 showed the strongest discriminating capacity for tuberculosis disease and in combination with IL-10 concentrations efficiently classified paucibacillary tuberculosis cases as well as those with fatal disease outcome. In addition, IL-6 and IP-10 levels decreased significantly after 6 weeks of treatment and analyses of subgroups with differential treatment response showed delayed decline of IL-6 levels in slow treatment responders. Conclusions: Combinations of different plasma cytokine (namely, IL-6, IL-10, and IP-10) efficiently classified tuberculosis patients with differential mycobacterial burden and especially IL-6 qualified as a biomarker candidate for early treatment response. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have shown unprecedented clinical benefit in cancer immunotherapy and are rapidly transforming the practice of advanced lung cancer. However, resistance routinely develops in patients treated with ICIs. We conducted this retrospective study to provide an overview on clinical characteristics of ICI resistance, optimal treatment beyond disease progression after prior exposure to immunotherapy, as well as potential prognostic factors of such resistance. Methods: 190 patients diagnosed with unresectable lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)/antiprogrammed cell death-ligand 1(PD-L1) at any treatment line at Zhongshan Hospital Fudan University between Sep 2017 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed. Levels of plasma cytokines were evaluated for the prognostic value of ICI resistance. Results: We found that EGFR/ALK/ROS1 mutation and receiving ICI treatment as second-line therapy were risk factors associated with ICI resistance. Patients with bone metastasis at baseline had a significantly shorter PFS1 time when receiving initial ICI treatment. Whether or not patients with oligo-progression received local treatment seemed to have no significant effect on PFS2 time. Systemic therapies including chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. TNF, IL-6 and IL-8 were significantly elevated when ICI resistance. Lower plasma TNF level and higher plasma IL-8 level seemed to be significantly associated with ICI resistance. A nomogram was established to prognosis the clinical outcome of patients treated with ICIs. Conclusion: Patients with EGFR/ALK/ROS1 mutation, or those receiving ICI treatment as second-line therapy had higher risk of ICI resistance. Patients with bone metastasis had poor prognosis during immunotherapy. For those patients with oligo-progression after ICI resistance, combination with local treatment did not lead to a significantly longer PFS2 time. Chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. Levels of plasma cytokines including TNF, IL-6 and IL-8 were associated with ICI resistance. [ABSTRACT FROM AUTHOR]

Background/Objectives: Psoriasis is a chronic, inflammatory, immuno-mediated cutaneous disease characterized by a prominent TNFα-IL23/IL17 immune axis. In recent years, targeted therapies have become standard practice for managing moderate-to-severe psoriasis and have demonstrated efficacy. At the same time, identifying factors associated with the success or failure of TNFα inhibitor therapy remains one of the most difficult aspects in psoriasis treatment. Methods: A clinical, non-randomized study was conducted to evaluate the impact of TNFα inhibitors on the plasma cytokine profiles in patients with moderate-to-severe psoriasis vulgaris (ICD-10 code L40.0). The patients were treated with either etanercept, adalimumab, or infliximab for 16 weeks. Plasma cytokine profiles were assessed using a BioPlex200 System. Results: By the 16th week of therapy, a positive treatment response (PASI ≥ 75) was observed in 51 patients (63%), while 30 patients (37%) showed no response (PASI ≤ 50). When using etanercept, a positive effect was observed in 11 patients (41%), in 14 patients (52%) using adalimumab, and in 26 patients (96%) using infliximab. Analysis of the baseline cytokine levels revealed no differences between the "positive effect" and "no effect" groups, except for IL20, which was 2.61 times higher in the "positive effect" group compared to the "no effect" group, suggesting its potential predictive role in the effectiveness of therapy with TNFα inhibitors. Treatment led to a decrease in IL17F, IL31, sCD40L, and VEGF for all patients, and in IL20 for the "positive effect" group. The increase in ICAM1 in the "no effect" group suggests the possible retention of active migration and the fixation of T cells in the affected skin in these patients. No significant difference in cytokine levels was observed when categorizing patients into subgroups based on the effectiveness of therapy with etanercept, infliximab, and adalimumab; only a pre- and post-treatment difference in the whole cohort was noted. A random forest model showed the importance of VEGF, sCD40L, and ICAM1. Conclusions: The baseline levels of VEGF, sCD40L, and ICAM1, as well as IL20, could serve as potential predictors of treatment effectiveness using TNFa inhibitors. However, this hypothesis requires confirmation with a larger patient population.

Background: Atherosclerosis is a chronic inflammatory disease. The balance between pro- and anti-inflammatory factors, acting on the arterial wall, promotes less or more coronary plaque macro-calcification, respectively. We investigated the association between monocyte phenotypic polarization and CTCA-assessed plaque dense-calcium volume (DCV) in patients with stable coronary artery disease (CAD). Methods: In 55 patients, individual DCV component was assessed by quantitative CTCA and normalized to total plaque volume. Flow cytometry expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1 and CXCR4 was quantified. Adhesion molecules and cytokines were measured by ELISA. Results: DCV values were significantly associated, by multiple regression analysis, with the expression (RFI) of CCR5 (p = 0.04), CX3CR1 (p = 0.03), CCR2 (p = 0.02), CD163 (p = 0.005) on all monocytes, and with the phenotypic M2-like polarization ratio, RFI CCR5/CD11b (p = 0.01). A positive correlation with the increased expression of chemokines receptors CCR2, CCR5 and CX3CR1 on subsets Mon1 was also present. Among cytokines, the ratio between IL-10 and IL-6 was found to be strongly associated with DCV (p = 0.009). Conclusions: The association between DCV and M2-like phenotypic polarization of circulating monocytes indicates that plaque macro-calcification in stable CAD may be partly modulated by an anti-inflammatory monocyte functional state, as evidenced by cell membrane receptor patterns. [ABSTRACT FROM AUTHOR]

Myelodysplastic syndrome (MDS) is characterized by activated inflammatory signaling and affects prognosis. Targeting inflammatory signaling may provide a way to treat the disease. We were curious whether there were changes in A20 in peripheral blood mononuclear cells (PBMC) of MDS patients. Therefore, we conducted a study with 60 clinical samples, including 30 MDS patients and 30 healthy controls. All patients with MDS were diagnosed and classified according to the criteria of the 2016 World Health Organization. The study was performed in accordance with the guidelines of the Declaration of Helsinki. Using Quantitative Real-Time RT-PCR, we discovered that A20 mRNA expression in PBMC of the MDS group was significantly lower than that in the control group ( P  < 0.001). Additionally, using Luminex Liquid Suspension Chip, we observed elevated plasma levels of pro-inflammatory IL-8 and TNF-α in the MDS group compared to the healthy control group ( P  < 0.001). We did not find a significant correlation between A20 mRNA and clinical characteristics (age, sex, concentration of hemoglobin, neutrophils count, platelets count, percent of blasts, and WHO classification) of the patients, nor between A20 mRNA and plasma cytokines (data not shown). Our study found down-regulated of A20 and increased levels of pro-inflammatory cytokines in the peripheral blood of MDS patients, providing further evidence for the activation of inflammatory signals in MDS.

Background: As per the 2017 WHO fact sheet, Coronary Artery Disease (CAD) is the primary cause of death in the world, and accounts for 31% of total fatalities. The unprecedented 17.6 million deaths caused by CAD in 2016 underscores the urgent need to facilitate proactive and accelerated pre-emptive diagnosis. The innovative and emerging Machine Learning (ML) techniques can be leveraged to facilitate early detection of CAD which is a crucial factor in saving lives. The standard techniques like angiography, that provide reliable evidence are invasive and typically expensive and risky. In contrast, ML model generated diagnosis is non-invasive, fast, accurate and affordable. Therefore, ML algorithms can be used as a supplement or precursor to the conventional methods. This research demonstrates the implementation and comparative analysis of K Nearest Neighbor (k-NN) and Random Forest ML algorithms to achieve a targeted "At Risk" CAD classification using an emerging set of 35 cytokine biomarkers that are strongly indicative predictive variables that can be potential targets for therapy. To ensure better generalizability, mechanisms such as data balancing, repeated k-fold cross validation for hyperparameter tuning, were integrated within the models. To determine the separability efficacy of "At Risk" CAD versus Control achieved by the models, Area under Receiver Operating Characteristic (AUROC) metric is used which discriminates the classes by exhibiting tradeoff between the false positive and true positive rates. Results: A total of 2 classifiers were developed, both built using 35 cytokine predictive features. The best AUROC score of.99 with a 95% Confidence Interval (CI) (.982,.999) was achieved by the Random Forest classifier using 35 cytokine biomarkers. The second-best AUROC score of.954 with a 95% Confidence Interval (.929,.979) was achieved by the k-NN model using 35 cytokines. A p-value of less than 7.481e-10 obtained by an independent t-test validated that Random Forest classifier was significantly better than the k-NN classifier with regards to the AUROC score. Presently, as large-scale efforts are gaining momentum to enable early, fast, reliable, affordable, and accessible detection of individuals at risk for CAD, the application of powerful ML algorithms can be leveraged as a supplement to conventional methods such as angiography. Early detection can be further improved by incorporating 65 novel and sensitive cytokine biomarkers. Investigation of the emerging role of cytokines in CAD can materially enhance the detection of risk and the discovery of mechanisms of disease that can lead to new therapeutic modalities. [ABSTRACT FROM AUTHOR]

Background: Atherosclerosis is a chronic inflammatory disease. The balance between pro- and anti-inflammatory factors, acting on the arterial wall, promotes less or more coronary plaque macro-calcification, respectively. We investigated the association between monocyte phenotypic polarization and CTCA-assessed plaque dense-calcium volume (DCV) in patients with stable coronary artery disease (CAD). Methods: In 55 patients, individual DCV component was assessed by quantitative CTCA and normalized to total plaque volume. Flow cytometry expression of CD14, CD16, CD18, CD11b, HLA-DR, CD163, CCR2, CCR5, CX3CR1 and CXCR4 was quantified. Adhesion molecules and cytokines were measured by ELISA. Results: DCV values were significantly associated, by multiple regression analysis, with the expression (RFI) of CCR5 (p = 0.04), CX3CR1 (p = 0.03), CCR2 (p = 0.02), CD163 (p = 0.005) on all monocytes, and with the phenotypic M2-like polarization ratio, RFI CCR5/CD11b (p = 0.01). A positive correlation with the increased expression of chemokines receptors CCR2, CCR5 and CX3CR1 on subsets Mon1 was also present. Among cytokines, the ratio between IL-10 and IL-6 was found to be strongly associated with DCV (p = 0.009). Conclusions: The association between DCV and M2-like phenotypic polarization of circulating monocytes indicates that plaque macro-calcification in stable CAD may be partly modulated by an anti-inflammatory monocyte functional state, as evidenced by cell membrane receptor patterns.

The 2017 World Health Organization Fact Sheet highlights that coronary artery disease is the leading cause of death globally, responsible for approximately 30% of all deaths. In this context, machine learning (ML) technology is crucial in identifying coronary artery disease, thereby saving lives. ML algorithms can potentially analyze complex patterns and correlations within medical data, enabling early detection and accurate diagnosis of CAD. By leveraging ML technology, healthcare professionals can make informed decisions and implement timely interventions, ultimately leading to improved outcomes and potentially reducing the mortality rate associated with coronary artery disease. Machine learning algorithms create non-invasive, quick, accurate, and economical diagnoses. As a result, machine learning algorithms can be employed to supplement existing approaches or as a forerunner to them. This study shows how to use the CNN classifier and RNN based on the LSTM classifier in deep learning to attain targeted "risk" CAD categorization utilizing an evolving set of 450 cytokine biomarkers that could be used as suggestive solid predictive variables for treatment. The two used classifiers are based on these "45" different cytokine prediction characteristics. The best Area Under the Receiver Operating Characteristic curve (AUROC) score achieved is (0.98) for a confidence interval (CI) of 95; the classifier RNN-LSTM used "450" cytokine biomarkers had a great (AUROC) score of 0.99 with a confidence interval of 0.95 the percentage 95, the CNN model containing cytokines received the second best AUROC score (0.92). The RNN-LSTM classifier considerably beats the CNN classifier regarding AUROC scores, as evidenced by a p -value smaller than 7.48 obtained via an independent t -test. As large-scale initiatives to achieve early, rapid, reliable, inexpensive, and accessible individual identification of CAD risk gain traction, robust machine learning algorithms can now augment older methods such as angiography. Incorporating 65 new sensitive cytokine biomarkers can increase early detection even more. Investigating the novel involvement of cytokines in CAD could lead to better risk detection, disease mechanism discovery, and new therapy options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Shoaib, Junaid, Husnain, Qadir, Ghadi, Askar and Abouhawwash.)

Background: Metabolic endotoxemia is considered a cause for high-fat diet (HFD)-induced inflammation. However, convincing experimental evidence in humans is scant.Objective: We determined whether a HFD or moderately HFD increases LPS and LPS-mediated cytokine production in the postprandial blood (PPB).Methods: Ninety-eight volunteers (age: 37.3 ± 1.5 y) from the cross-sectional phenotyping study (PS) and 62 volunteers (age: 26.8 ± 1.2 y) from the intervention study (IS) consumed a breakfast containing 60% kcal fat (HF) and 36% kcal fat (moderately HF), respectively. For the IS, only the results from the placebo group are presented. Blood samples were probed for LPS-mediated cytokine production by incubating them with LPS inhibitor polymyxin B (PMB) for 24 h at 37°C besides the Limulus amebocyte lysate (LAL) assay. Repeated-measures ANOVA was used to compare the temporal changes of metabolic profiles and treatment outcomes.Results: At least 87.5% of the plasma LPS measurements in 32 PS volunteers from each time point were below the LAL assay sensitivity (0.002 EU/mL). PMB suppressed IL-1β (P = 0.035) and IL-6 (P = 0.0487) production in the 3 h PPB of the PS after 24 h incubation at 37°C compared to the vehicle control, suggesting the presence of LPS. However, the amount of LPS did not increase the cytokine concentrations in the 3 h PPB above the fasting concentrations. Such suppression was not detected in the PPB of the IS. Treating whole blood with lipoprotein lipase (LPL) significantly (P < 0.05) increased FFA and cytokine (IL-1β, IL-6, TNF-α) concentrations in both studies.Conclusion: LPS may not be the major cause of postprandial inflammation in healthy adults consuming a moderately HF meal (36% kcal fat, similar to the typical American diet) or a HF meal (60% kcal fat). Plasma FFAs may modulate postprandial inflammation. The prevailing concept of HFD-induced metabolic endotoxemia requires careful re-evaluation. The PS was registered at clinicaltrials.gov as NCT02367287 and the IS as NCT02472171. [ABSTRACT FROM AUTHOR]

• Plasma cytokines were assessed in children with autism and their siblings. • Plasma G-CSF was associated with an increased risk of being diagnosed as an ASD. • The overall cytokine profile of siblings and ASD children was very similar. • There is a need to consider if the controls are siblings of ASD children or not. Several studies of autism spectrum disorder (ASD) have shown cytokine dysregulation in children with ASD, leading to a consideration of the immune theory of the ASD etiopathogenesis and a debate about cytokines as potential biomarkers of ASD. However, the results of these studies are still inconsistent. Overall, studies comparing the cytokine levels of children with ASD and neurotypical siblings achieved relatively different results than studies with control groups of non-siblings. The studies suggest that the immune profile of siblings of individuals with ASD serving as control is more similar to children with ASD than the profile of non-siblings. However, there are still only a few studies with control groups including neurotypical siblings of children with ASD. The aim of our study was to determine whether the concentration of plasma cytokine levels may differentiate children with ASD from their neurotypical siblings. The sample consisted of 40 children with ASD (mean age 7.11 years, SD 2.9) and 21 neurotypical siblings (mean age 7.38, SD 3.3). Levels of 20 cytokines were included into the statistical analysis. A multiple logistic regression model using multiple corrections showed that an increase in log-transformed plasma G-CSF (granulocyte colony stimulating factor) concentration is associated with an increased risk of the child being diagnosed as an ASD case (OR = 4.35, 95% CI 1.77, 10.73). Although the significantly increased concentration of G-CSF suggests a slightly different activity of the immune system of children with ASD, the overall cytokine profile of their siblings appeared to be very similar. [ABSTRACT FROM AUTHOR]

Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and plays a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS). It has been implicated as driver of disease progression and is observed in ALS patients, as well as in the transgenic SOD1G93A mouse model. Here, we explore and validate the therapeutic potential of the d-enantiomeric peptide RD2RD2 upon oral administration in SOD1G93A mice. Transgenic mice were treated daily with RD2RD2 or placebo for 10 weeks and phenotype progression was followed with several behavioural tests. At the end of the study, plasma cytokine levels and glia cell markers in brain and spinal cord were analysed. Treatment resulted in a significantly increased performance in behavioural and motor coordination tests and a decelerated neurodegenerative phenotype in RD2RD2-treated SOD1G93A mice. Additionally, we observed retardation of the average disease onset. Treatment of SOD1G93A mice led to significant reduction in glial cell activation and a rescue of neurons. Analysis of plasma revealed normalisation of several cytokines in samples of RD2RD2-treated SOD1G93A mice towards the levels of non-transgenic mice. In conclusion, these findings qualify RD2RD2 to be considered for further development and testing towards a disease modifying ALS treatment.

Acclimation to heat or hypoxic stress activates the heat shock response and accumulation of cytoprotective heat shock proteins (HSPs). By inhibiting the NF-κB pathway HSP72 can preserve epithelial function and reduce systemic inflammation. The aim of this study was to determine the time course of mHSP72 accumulation during acclimation, and to assess intestinal barrier damage and systemic inflammation following hypoxic exercise. Three groups completed 10 × 60-min acclimation sessions (50% normoxic VO2peak) in control (n = 7; 18°C, 35% RH), hypoxic (n = 7; FiO2 = 0.14, 18°C, 35% RH), or hot (n = 7; 40°C, 25% RH) conditions. Tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 10 (IL-10), and intestinal fatty acid binding protein (I-FABP) were determined at rest and following a cycling normoxic stress test (NST; ~2 weeks before acclimation), pre-acclimation hypoxic stress test (HST1; FiO2 = 0.14, both at 50% normoxic VO2peak; ~1 week before acclimation) and post-acclimation HST (48 h; HST2). Monocyte HSP72 (mHSP72) was determined before and after exercise on day 1, 3, 5, 6, and 10 of acclimation. Accumulation of basal mHSP72 was evident from day 5 (p < 0.05) of heat acclimation and increased further on day 6 (p < 0.01), and day 10 (p < 0.01). In contrast, basal mHSP72 was elevated on the final day of hypoxic acclimation (p < 0.05). Following the NST, plasma TNF-α (–0.11 ± 0.27 ng.mL−1), IL-6 (+0.62 ± 0.67 ng.mL−1) IL-10 (+1.09 ± 9.06 ng.mL−1) and I-FABP (+37.6 ± 112.8 pg.mL−1) exhibited minimal change. After HST1, IL-6 (+3.87 ± 2.56 ng.mL−1), IL-10 (+26.15 ± 26.06 ng.mL−1) and I-FABP (+183.7 ± 182.1 pg.mL−1) were elevated (p < 0.01), whereas TNF-α was unaltered (+0.08 ± 1.27; p > 0.05). A similar trend was observed after HST2, with IL-6 (+3.09 ± 1.30 ng.mL−1), IL-10 (+23.22 ± 21.67 ng.mL−1) and I-FABP (+145.9 ±123.2 pg.mL−1) increased from rest. Heat acclimation induces mHSP72 accumulation earlier and at a greater magnitude compared to matched work hypoxic acclimation, however neither acclimation regime attenuated the systemic cytokine response or intestinal damage following acute exercise in hypoxia.

Background and Aim: Long-term immune alterations have been proposed to play a mechanistic role in posttraumatic stress disorder (PTSD) as well as in its associated increase in medical morbidity and mortality. Better characterization of altered immune function may help identify diagnostic and prognostic biomarkers and potentially targets for preventive intervention. Methods: As part of an ongoing study, we conducted a preliminary case-control comparison of resting immune inflammatory profiles between terror victims treated in childhood at the emergency department over the previous decade, who developed chronic PTSD upon long-term follow-up, and healthy controls. Results: Our preliminary results in a subsample of this ongoing study support and extend elevated resting levels of granulocyte colony-stimulating factor, interleukin-4, and regulated on activation, normal T cell expressed and secreted in childhood onset chronic PTSD. Conclusion: Chronic immune alterations may participate in inflammatory activation and signal to the CNS through the neurovascular unit, as well as modulate the neuroendocrine axis. Better characterization and understanding of these preliminary findings may point to diagnostic and prognostic biomarkers and potentially elucidate mechanistic involvement of immune activation in PTSD. [ABSTRACT FROM AUTHOR]

Acclimation to heat or hypoxic stress activates the heat shock response and accumulation of cytoprotective heat shock proteins (HSPs). By inhibiting the NF-kB pathway HSP72 can preserve epithelial function and reduce systemic inflammation. The aim of this study was to determine the time course of mHSP72 accumulation during acclimation, and to assess intestinal barrier damage and systemic inflammation following hypoxic exercise. Three groups completed 10 × 60-min acclimation sessions (50% normoxic VO2peak) in control (n = 7; 18◦C, 35% RH), hypoxic (n = 7; FiO2 = 0.14, 18◦C, 35% RH), or hot (n = 7; 40◦C, 25% RH) conditions. Tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), interleukin 10 (IL-10), and intestinal fatty acid binding protein (I-FABP) were determined at rest and following a cycling normoxic stress test (NST; ∼2 weeks before acclimation), pre-acclimation hypoxic stress test (HST1; FiO2 = 0.14, both at 50% normoxic VO2peak; ∼1 week before acclimation) and post-acclimation HST (48 h; HST2). Monocyte HSP72 (mHSP72) was determined before and after exercise on day 1, 3, 5, 6, and 10 of acclimation. Accumulation of basal mHSP72 was evident from day 5 (p < 0.05) of heat acclimation and increased further on day 6 (p < 0.01), and day 10 (p < 0.01). In contrast, basal mHSP72 was elevated on the final day of hypoxic acclimation (p < 0.05). Following the NST, plasma TNF-a (–0.11 ± 0.27 ng.mL−1), IL-6 (+0.62 ± 0.67 ng.mL−1) IL-10 (+1.09 ± 9.06 ng.mL−1) and I-FABP (+37.6 ± 112.8 pg.mL−1) exhibited minimal change. After HST1, IL-6 (+3.87 ± 2.56 ng.mL−1), IL-10 (+26.15 ± 26.06 ng.mL−1) and I-FABP (+183.7 ± 182.1 pg.mL−1) were elevated (p < 0.01), whereas TNF-a was unaltered (+0.08 ± 1.27; p > 0.05). A similar trend was observed after HST2, with IL-6 (+3.09 ± 1.30 ng.mL−1), IL-10 (+23.22 ± 21.67 ng.mL−1) and I-FABP (+145.9 ±123.2 pg.mL−1) increased from rest. Heat acclimation inducesmHSP72 accumulation earlier and at a greatermagnitude compared tomatched work hypoxic acclimation, however neither acclimation regime attenuated the systemic cytokine response or intestinal damage following acute exercise in hypoxia. [ABSTRACT FROM AUTHOR]

Background: Immune checkpoint inhibitors (ICIs) have shown unprecedented clinical benefit in cancer immunotherapy and are rapidly transforming the practice of advanced lung cancer. However, resistance routinely develops in patients treated with ICIs. We conducted this retrospective study to provide an overview on clinical characteristics of ICI resistance, optimal treatment beyond disease progression after prior exposure to immunotherapy, as well as potential prognostic factors of such resistance., Methods: 190 patients diagnosed with unresectable lung cancer who received at least one administration of an anti-programmed cell death 1 (PD-1)/anti-programmed cell death-ligand 1(PD-L1) at any treatment line at Zhongshan Hospital Fudan University between Sep 2017 and December 2019 were enrolled in our study. Overall survival (OS) and progression-free survival (PFS) were analyzed. Levels of plasma cytokines were evaluated for the prognostic value of ICI resistance., Results: We found that EGFR/ALK/ROS1 mutation and receiving ICI treatment as second-line therapy were risk factors associated with ICI resistance. Patients with bone metastasis at baseline had a significantly shorter PFS1 time when receiving initial ICI treatment. Whether or not patients with oligo-progression received local treatment seemed to have no significant effect on PFS2 time. Systemic therapies including chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. TNF, IL-6 and IL-8 were significantly elevated when ICI resistance. Lower plasma TNF level and higher plasma IL-8 level seemed to be significantly associated with ICI resistance. A nomogram was established to prognosis the clinical outcome of patients treated with ICIs., Conclusion: Patients with EGFR/ALK/ROS1 mutation, or those receiving ICI treatment as second-line therapy had higher risk of ICI resistance. Patients with bone metastasis had poor prognosis during immunotherapy. For those patients with oligo-progression after ICI resistance, combination with local treatment did not lead to a significantly longer PFS2 time. Chemotherapy and anti-angiogenic therapy rather than continued immunotherapy beyond ICI resistance had significant effect on PFS2 time. Levels of plasma cytokines including TNF, IL-6 and IL-8 were associated with ICI resistance., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhou, Lu, Zhu, Ding, Zhang, Xu, Gao, Zhou, Song and Hu.)

Purpose: Hypocitrullinemia has been suggested to be a prognostic factor for patients in intensive care. The aim of this ancillary study of the Corticosteroids and Intensive Insulin Therapy for Septic Shock prospective study was to investigate plasma L-citrulline concentrations and its relationship with inflammation and digestive bacterial translocation in patients with septic shock multiorgan failure and without primary intestinal disease or chronic renal failure. Methods: Sixteen adult patients were selected. They were studied on day (D) 0 at hours (H) 0, 6, 12, 18, and 24 and on D4 (H96). Selected plasma amino acids and proteins, proinflammatory (tumor necrosis factor α [TNF-α]) and anti-inflammatory (interleukin [IL] 10) cytokine concentrations, and bacterial translocation were measured. Results: Eight D14 survivors and 8 D14 nonsurvivors patients were studied. Citrulline was decreased on D0 (H0: 29 ± 10 vs nadir: 18 ± 6 μmol/L; P < .05). The citrulline nadir was lower (P < .01) in patients with digestive bacterial translocation than that in those without. Mean citrulline concentrations at H0 to H96 were not significantly different between survivors and nonsurvivors. In both groups, citrulline was significantly inversely correlated with C-reactive protein (r2=0.10, P < .01) on D0. No significant correlations were found between citrulline and albumin, transthyretin, TNF-α, IL-10, or TNF-α/IL-10 ratio. Conclusions: At the onset of septic shock, plasma citrulline decreases and varies inversely with C-reactive protein and is lower when digestive bacterial translocation occurs. This finding could reflect an early acute intestinal dysfunction, but measurement of citrulline concentration does not appear to be able to predict the patients' mortality. [ABSTRACT FROM AUTHOR]

Abstract: Effects of 14 consecutive day exposure to desipramine (10mg/kg i.p.), by itself or following chronic open field (OF) exposure, on subsequent neuroimmunological effects of acute (30min) OF stress and the involvement of individual differences in response to novelty or social position in the anti-depressive responsiveness were investigated. Chronic desipramine pretreatment did not protect against OF stress-induced suppression of blood anti-tumor natural killer cell activity but increased plasma interleukin-10 and decreased interferon-γ and corticosterone concentration. These effects were particularly dangerous for the animals with increased responsivity to stress (desipramine alone) or with low behavioral activity (desipramine after chronic stress). [Copyright &y& Elsevier]

Although both human epidemiologic and animal model studies have suggested that caffeine/coffee protects against Alzheimer's disease, direct human evidence for this premise has been lacking. In the present case-control study, two separate cohorts consisting of 124 total individuals (65-88 years old) were cognitively assessed and a blood sample taken for caffeine/biomarker analysis. Subjects were then monitored for cognitive status over the ensuing 2-4 year period to determine the extent to which initial plasma caffeine/biomarkers levels would be predictive of changes in cognitive status. Plasma caffeine levels at study onset were substantially lower (-51%) in mild cognitive impairment (MCI) subjects who later progressed to dementia (MCI→DEM) compared to levels in stable MCI subjects (MCI→MCI). Moreover, none of the MCI→DEM subjects had initial blood caffeine levels that were above a critical level of 1200 ng/ml, while half of stable MCI→MCI subjects had blood caffeine levels higher than that critical level. Thus, plasma caffeine levels greater than 1200 ng/ml (≈6 μM) in MCI subjects were associated with no conversion to dementia during the ensuing 2-4 year follow-up period. Among the 11 cytokines measured in plasma, three of them (GCSF, IL-10, and IL-6) were decreased in MCI→DEM subjects, but not in stable MCI→MCI subjects with high plasma caffeine levels. Coffee would appear to be the major or perhaps only source of caffeine for such stable MCI patients. This case-control study provides the first direct evidence that caffeine/coffee intake is associated with a reduced risk of dementia or delayed onset, particularly for those who already have MCI. [ABSTRACT FROM AUTHOR]

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL-1 receptor antagonist and increasing monocyte activation early post-transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long-term graft survival. We compared pre-transplant, early post-transplant, and late post-transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post-transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin-6 (IL-6) receptor (R) (p = 0.002; p = 0.001), and IL-10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post-transplant, plasma neopterin (p < 0.001) and IL-10 (p < 0.001) were higher in DGF than IGF patients. Three days post-transplant, the results indicated reduced sIL-1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL-6R and IL-10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL-6R and IL-10. Lower sIL-1 production in DGF than IGF patients early post-transplant might promote the increased production of monocyte-derived neopterin, sIL-6R, and IL-10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome. [ABSTRACT FROM AUTHOR]

The article presents a study which investigates the level of immune activation in human immunodeficiency virus (HIV) uninfected and HIV-infected individuals after antiretroviral treatment (ART) in sub-Saharan Africa. It was found out that tumor necrosis factor, monocyte chemotactic protein-1, and IL-1 receptor antagonist were higher in HIV infected individuals than the HIV-uninfected people. In addition, it shows that ART decreases cytokines close to the levels of the HIV-uninfected individuals.

Myeloablative conditioning regimens commonly lead to prolonged anorexia and poor oral intake. In a prospective study of 147 patients receiving CY, total body irradiation and allogeneic hematopoietic cells, we determined the extent of decline in oral intake and assessed plasma cytokine levels and development of acute GVHD as explanations for protracted anorexia. For each patient, daily oral caloric intake was expressed as a percent of estimated basal requirements, calculated as basal energy expenditure, through day 20. Oral caloric intake was significantly reduced in 92% of patients and remained low. The nadir in oral intake occurred at days 10–12, when median oral caloric intake was 3% of basal energy requirements. Plasma cytokines known to affect appetite (IL2, IL6, tumor necrosis factor-alpha) were significantly elevated above normal following conditioning therapy (P<0.001 for each cytokine). Acute GVHD did not appear to affect oral intake to transplant day 20 in this cohort of patients; however, plasma levels of IL6 rose steeply before the clinical onset of GVHD. Persistent fever occurred with the greatest frequency in patients with most profound reduction in oral intake. We conclude that prolonged alterations in oral intake following this myeloablative regimen may be related to circulating cytokines known to alter eating behavior.Bone Marrow Transplantation (2007) 40, 765–772; doi:10.1038/sj.bmt.1705816; published online 13 August 2007 [ABSTRACT FROM AUTHOR]

Abstract Objective: In other studies, we have found deviant functions in peripheral neutrophils in periodontitis. The aim here was to study (1) the release of cytokines, IL-8 and TNFα, from neutrophils in 15 treated periodontitis patients and pair-matched controls as well as (2) the effects of cigarette smoking. Material and methods: Cytokines released in the incubation medium from un-stimulated and Fcγ-R-stimulated neutrophils and some acute-phase reactants were measured with ELISA. Results: Non-smoking patients had trends for lower TNFα release compared to non-smoking controls, while corresponding trends were rather similar for Il-8. Smoking had a moderate but inconsistent effect on the release of both cytokines. However, in patients, the ratio between stimulated/un-stimulated release of Il-8 was significantly lowered by smoking (p <0.03). The parameters of inflammation in plasma differed only slightly between patients and controls, indicating that periodontal disease in a quiet phase has a negligible systemic effect with the possible exception for a higher IL-8 level. In contrast, smoking had significant systemic effect on the neutrophil count and IgG levels. Conclusions: Release of IL-8 and TNF-α from peripheral neutrophils and various parameters of inflammation in plasma seem to be affected more by cigarette smoking than periodontal disease. [ABSTRACT FROM AUTHOR]

Background: Lipusu is the first commercialized liposomal formulation of paclitaxel and has demonstrated promising efficacy against locally advanced lung squamous cell carcinoma (LSCC) in a small-scale study. Here, we conducted a multicenter, randomized, phase 3 study to compare the efficacy and safety of cisplatin plus Lipusu (LP) versus cisplatin plus gemcitabine (GP) as first-line treatment in locally advanced or metastatic LSCC., Methods: Patients enrolled were aged between 18 to 75 years, had locally advanced (clinical stage IIIB, ineligible for concurrent chemoradiation or surgery) or metastatic (Stage IV) LSCC, had no previous systemic chemotherapy and at least one measurable lesion as per the Response Evaluation Criteria in Solid Tumors (version 1.1) before administration of the trial drug. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety profiles. To explore the possible predictive value of plasma cytokines for LP treatment, plasma samples were collected from the LP group at baseline and first efficacy evaluation time and were then subjected to analysis by 45-Plex ProcartaPlex Panel 1 to detect the presence of 45 cytokines using the Luminex xMAP technology. The correlation between treatment outcomes and dynamic changes in the levels of cytokines were evaluated in preliminary analyses., Results: The median duration of follow-up was 15.4 months. 237 patients in the LP group and 253 patients in the GP group were included in the per protocol set (PPS). In the PPS, the median PFS was 5.2 months versus 5.5 months in the LP and GP group (hazard ratio [HR]: 1.03, P = 0.742) respectively. The median OS was 14.6 months versus 12.5 months in the LP and GP group (HR: 0.83, P = 0.215). The ORR (41.8% versus 45.9%, P = 0.412) and DCR (90.3% versus 88.1%, P = 0.443) were also similar between the LP and GP group. A significantly lower proportion of patients in the LP group experienced adverse events (AEs) leading to treatment interruptions (10.9% versus 26.4%, P < 0.001) or treatment termination (14.3% versus 23.1%, P = 0.011). The analysis of cytokine levels in the LP group showed that low baseline levels of 27 cytokines were associated with an increased ORR, and 15 cytokines were associated with improved PFS, with 14 cytokines, including TNF-α, IFN-γ, IL-6, and IL-8, demonstrating an overlapping trend., Conclusion: The LP regimen demonstrated similar PFS, OS, ORR and DCR as the GP regimen for patients with locally advanced or metastatic LSCC but had more favorable toxicity profiles. The study also identified a spectrum of different cytokines that could be potentially associated with the clinical benefit in patients who received the LP regimen., (© 2021 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Neuroinflammation is a pathological hallmark of several neurodegenerative disorders and plays a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS). It has been implicated as driver of disease progression and is observed in ALS patients, as well as in the transgenic SOD1G93A mouse model. Here, we explore and validate the therapeutic potential of the d-enantiomeric peptide RD2RD2 upon oral administration in SOD1G93A mice. Transgenic mice were treated daily with RD2RD2 or placebo for 10 weeks and phenotype progression was followed with several behavioural tests. At the end of the study, plasma cytokine levels and glia cell markers in brain and spinal cord were analysed. Treatment resulted in a significantly increased performance in behavioural and motor coordination tests and a decelerated neurodegenerative phenotype in RD2RD2-treated SOD1G93A mice. Additionally, we observed retardation of the average disease onset. Treatment of SOD1G93A mice led to significant reduction in glial cell activation and a rescue of neurons. Analysis of plasma revealed normalisation of several cytokines in samples of RD2RD2-treated SOD1G93A mice towards the levels of non-transgenic mice. In conclusion, these findings qualify RD2RD2 to be considered for further development and testing towards a disease modifying ALS treatment. [ABSTRACT FROM AUTHOR]

Introduction: Trypanosoma brucei (T.b.) rhodesiense is the cause of the acute form of human African trypanosomiasis (HAT) in eastern and southern African countries, including Malawi. For a long time, untreated HAT infections were believed to be 100% fatal. However, recent studies show that infection by T.b. rhodesiense can result in a wide range of clinical outcomes in its human host. Apart from other factors such as parasite diversity, cytokines have been strongly implicated to play a major role in the outcome of T.b. rhodesiense infections.In this study, we quantify the levels of three cytokines Interleukin-8 (IL-8), Tumor Necrotic Factor alpha (TNF-α) and Interleukin -10 (IL-10) in plasma amongst HAT cases (treated and untreated) and controls recruited during medical survey., Methods: Two-hundred and thirty-three plasma samples (HAT cases and controls) from Rumphi, one of the endemic areas in Malawi were used. Blood collected was centrifuged, plasma extracted and stored in cryovials at -80°C until processing. Plasma cytokine concentration was measured using ELISA., Results: Plasma samples for 233 individuals, 76 HAT cases and 157 controls were quantified. Among the cases, nine had their plasma collected before treatment (untreated) and the rest were treated before blood for plasma analysis was collected. Controls had significantly higher mean plasmatic levels of TNF-α (94.5 ±474.12 pg/ml) and IL-8 (2258.6 ±5227.4 pg/ml) than cases TNF-α (29.35±181.58 pg/ml) and IL-8 (1191.3±4236.09 pg/ml). Controls and cases had similar mean levels of IL-10 in plasma. Only IL-8 had statistically significant higher median levels in the untreated than treated HAT cases P=0.006., Conclusion: Our data suggest that cytokines could be considered as biomarkers of HAT infection and treatment. Further studies with a larger cohort of cases and additional cytokines which are known to be associated with HAT infection outcomes will be required to evaluate these cytokines further., (© 2021 The College of Medicine and the Medical Association of Malawi.)

Background: Recovery from training is vital as it ensures training and performance to continue at high intensities and longer durations to stimulate the body and cause further adaptations., Objective: To evaluate different methods of post-workout recovery in Paralympic powerlifting athletes., Methods: Twelve male athletes participated (25.4 ± 3.3 years; 70.3 ± 12.1 kg). The presence of muscle edema, pain threshold, plasma cytokines, and performance measurement were evaluated five times. The recovery methods used in this study were passive recovery (PR), dry needling (DN), and cold-water immersion (CWI)., Results: The data analysis showed that the maximal force decreased compared to the pretest value at 15 min and 2 h. The results also revealed that CWI and DN increased Interleukin 2 (IL-2) levels from 24 to 48 h more than that from 2 h to 24 h. After DN, muscle thickness did not increase significantly in any of the muscles, and after 2 h, muscle thickness decreased significantly again in the major pectoralis muscle. After CWI, pain pressure stabilized after 15 min and increased significantly again after 2 h for acromial pectoralis., Conclusion: The strength training sessions generate several changes in metabolism and different recovery methods contribute differently to maintain homeostasis in Paralympic powerlifting athletes.

• iRM patients show a strong persistent cytotoxic NK cell response and activated Th1 and Th2 type lymphocytes in the blood. • Plasma levels of immunosuppressive Th2 type cytokines are low in iRM patients. • In-vitro, NK cells of iRM patients show a strong consumption of TGF-ß1 that might contribute to the low systemic Th2 type plasma levels. • iRM patients do not show a systemic switch to a Th2 type cytokine pattern. • It would be worth thinking about an earlier start of immunosuppressive therapy in iRM patients. The present review article compares NK cell subsets and cytokine patterns determined in the peripheral blood as well as results of functional in-vitro assays using peripheral NK cells of idiopathic recurrent miscarriage (iRM) patients with corresponding results obtained in female healthy controls and female renal transplant recipients with good long-term graft function. Immune mechanisms, inducing transplant rejection in long-term transplant recipients might also be able to induce rejection of semi-allogeneic fetal cells in patients with iRM. Consequently, the immune status of transplant recipients with good stable long-term graft function should be different from the immune status of iRM patients. iRM patients show a strong persistent cytotoxic NK cell response in the periphery. Simultaneously, immunostimulatory Th1 as well as immunosuppressive Th2 type lymphocytes in the blood are strongly activated but plasma levels of immunosuppressive Th2 type cytokines are abnormally low. In-vitro, unstimulated NK cell cultures of iRM patients show a strong spontaneous TGF-ß1 release in the supernatant but lower TGF-ß1 levels after stimulation with tumor cell line K562, suggesting strong consumption of TGF-ß1 by pre-activated NK cells of iRM patients that might contribute to the low systemic Th2 type plasma levels. iRM patients do not show a systemic switch to a Th2 type cytokine pattern and one might hypothesize that low TGF-ß plasma levels indicate low TGF-ß levels in the micromilieu immediately before fetal rejection. Persistent TGF-ß deficiency implies a persistent unfavorable micromilieu for pregnancy resulting in failing tolerance induction due to lack of TGF-ß, a condition that might contribute to iRM. [ABSTRACT FROM AUTHOR]

We determined the intra- and postoperative plasma concentrations of cytokines (tumor necrosis factor [TNF]-Α, interleukin [IL]-1Β, IL-6, and IL-8) in oral surgery patients with procedures ranging in duration from 20 to 375 min and investigated their relationship to the intensity of the surgical stress over time. No significant differences from baseline levels were observed in the levels of TNF-Α, IL-1Β, and IL-8. By contrast, increased IL-6 levels were noted only on the first postoperative day, when they reached 1500% of the baseline level, after which they decreased to preoperative levels by the third postoperative day and tended to reflect the intensity of surgical stress. [ABSTRACT FROM AUTHOR]

Objective: This study investigated changes of plasma cytokines and aimed to build a dynamic nomogram for diabetic macular edema (DME) in type 2 diabetes mellitus (T2DM)., Methods: In a pilot cohort, plasma samples were selected from 9 T2DM patients and 9 DME patients to screen for cytokine differences. The screening cytokines were then validated by enzyme-linked immunoassay in a cohort, which contained 100 DME (DME group) and 100 T2DM patients without DME (T2DM group). A dynamic nomogram for predicting DME was developed, based on the plasma cytokines., Results: In the pilot cohort, 11 plasma cytokines were significantly increased in the DME group. In the validation cohort, platelet-derived growth factor (PDGF)-BB, tissue inhibitors of metalloproteinase (TIMP)-1, angiopoietin (ANG-1), and vascular endothelial cell growth factor receptor (VEGFR)-2 were confirmed to be significantly elevated in the DME group. The dynamic nomogram demonstrated good calibration and discrimination, with an area under the receiver operating characteristic curve (AUC) of 0.88. In the test set, sensitivity, specificity, and AUC were 73.3%, 80.0%, and 0.84, respectively., Conclusion: Plasma cytokines were closely associated with DME. A novel dynamic monogram including ANG-1, PDGF-BB, TIMP-1, and VEGFR2 was a novel tool for predicting DME.

Aims: This study aimed to investigate changes of plasma cytokines and to develop machine learning classifiers for predicting non-proliferative diabetic retinopathy among type 2 diabetes mellitus patients., Results: There were 12 plasma cytokines significantly higher in the non-proliferative diabetic retinopathy group in the pilot cohort. The validation cohort showed that angiopoietin 1, platelet-derived growth factor-BB, tissue inhibitors of metalloproteinase 2 and vascular endothelial growth factor receptor 2 were significantly higher in the NPDR group. Machine learning algorithms using the random forest yielded the best performance, with sensitivity of 92.3%, specificity of 75%, PPV of 82.8%, NPV of 88.2% and area under the curve of 0.84., Conclusions: Plasma angiopoietin 1, platelet-derived growth factor-BB, and vascular endothelial growth factor receptor 2 were associated with presence of non-proliferative diabetic retinopathy and may be good biomarkers that play important roles in pathophysiology of diabetic retinopathy., Materials and Methods: In pilot cohort, 60 plasma cytokines were simultaneously measured. In validation cohort, angiopoietin 1, CXC-chemokine ligand 16, platelet-derived growth factor-BB, tissue inhibitors of metalloproteinase 1, tissue inhibitors of metalloproteinase 2, and vascular endothelial growth factor receptor 2 were validated using ELISA kits. Machine learning algorithms were developed to build a prediction model for non-proliferative diabetic retinopathy.

Background and Aim: Long-term immune alterations have been proposed to play a mechanistic role in posttraumatic stress disorder (PTSD) as well as in its associated increase in medical morbidity and mortality. Better characterization of altered immune function may help identify diagnostic and prognostic biomarkers and potentially targets for preventive intervention., Methods: As part of an ongoing study, we conducted a preliminary case-control comparison of resting immune inflammatory profiles between terror victims treated in childhood at the emergency department over the previous decade, who developed chronic PTSD upon long-term follow-up, and healthy controls., Results: Our preliminary results in a subsample of this ongoing study support and extend elevated resting levels of granulocyte colony-stimulating factor, interleukin-4, and regulated on activation, normal T cell expressed and secreted in childhood onset chronic PTSD., Conclusion: Chronic immune alterations may participate in inflammatory activation and signal to the CNS through the neurovascular unit, as well as modulate the neuroendocrine axis. Better characterization and understanding of these preliminary findings may point to diagnostic and prognostic biomarkers and potentially elucidate mechanistic involvement of immune activation in PTSD., (© 2018 S. Karger AG, Basel.)