Search

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual's susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings. [ABSTRACT FROM AUTHOR]

Interleukins (ILs) are vital in regulating the immune system, enabling to combat fungal diseases like candidiasis effectively. Their inhibition may cause enhanced susceptibility to infection. IL inhibitors have been employed to control autoimmune diseases and inhibitors of IL-17 and IL-23, for example, have been associated with an elevated risk of Candida infection. Thus, applying IL inhibitors might impact an individual’s susceptibility to Candida infections. Variations in the severity of Candida infections have been observed between individuals with different IL inhibitors, necessitating careful consideration of their specific risk profiles. IL-1 inhibitors (anakinra, canakinumab, and rilonacept), IL-2 inhibitors (daclizumab, and basiliximab), and IL-4 inhibitors (dupilumab) have rarely been associated with Candida infection. In contrast, tocilizumab, an inhibitor of IL-6, has demonstrated an elevated risk in the context of coronavirus disease 2019 (COVID-19) treatment, as evidenced by a 6.9% prevalence of candidemia among patients using the drug. Furthermore, the incidence of Candida infections appeared to be higher in patients exposed to IL-17 inhibitors than in those exposed to IL-23 inhibitors. Therefore, healthcare practitioners must maintain awareness of the risk of candidiasis associated with using of IL inhibitors before prescribing them. Future prospective studies need to exhaustively investigate candidiasis and its associated risk factors in patients receiving IL inhibitors. Implementing enduring surveillance methods is crucial to ensure IL inhibitors safe and efficient utilization of in clinical settings.

Neurological infections are often devastating in their clinical presentation. Although significant advances have made in neuroimaging techniques and molecular tools for diagnosis, as well as in anti-infective therapy, these diseases always difficult to diagnose and treat. Neuroparasitic infections and virus infections lead to neurological infections. In the nervous system, various cytokines and chemokines act as neuroinflammatory agents, neuromodulators, regulate neurodevelopment, and synaptic transmission. Among the most important cytokines, interleukins (ILs) are a large group of immunomodulatory proteins that elicit a wide variety of responses in cells and tissues. These ILs are involved in pro and anti-inflammatory effects, systemic inflammation, immune system modulation and play crucial roles in fighting cancer, infectious disease, and neurological disorders. Interleukin-34 (IL-34) identified by screening a comprehensive human protein library containing ∼3400 secreted and extracellular domain proteins in a human monocyte viability assay. Recent evidence has disclosed the crucial roles of IL-34 in the proliferation and differentiation of mononuclear phagocyte lineage cells, osteoclastogenesis, and inflammation. Additionally, IL-34 plays an important role in development, homeostasis, and disease. Dysregulation in IL-34 function can lead to various inflammatory and infectious diseases (e.g. Inflammatory bowel disease, liver fibrosis, Systemic Lupus erythematosus, rheumatoid arthritis), neurological disorders (e.g. Alzheimer disease) and neurological infectious disease (e.g. West Nile virus disease). In this review, we explore the biological role of IL-34 in addition to various impairments caused by dysregulation in IL-34 and discuss their potential links that may lead to important therapeutic and/or preventive strategies for these disorders. [ABSTRACT FROM AUTHOR]

Abstract Background Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection. Methods This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR. Results Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (p

Interleukins are signaling molecules involved in the immune system, and they play a variety of roles in different diseases and cancers. Acute myeloid leukemia (AML) is the most common type of leukemia in adults, and survival rate after diagnosis is very low. Investigating the role interleukins play in AML can help understand the progression of the disease. There exists a need for more effective treatment of AML. Interleukins can be used to guide immunotherapy for AML. This review article will examine how specific interleukins play a role in AML disease progression and how they can be utilized as a future treatment option. [ABSTRACT FROM AUTHOR]

Background: Pneumocystis pneumonia (PCP) is a fatal infectious disease caused by Pneumocystis jirovecii (PJP). The major factor relevant to morbidity and mortality seems to be the host inflammatory reaction. The objective of this study was to evaluate the role of IL-2, IL-4, IL-10, and IL-13 cytokine mRNA expression among suspected P. jirovecii infection.Methods: This was a cross-sectional analytical study undertaken in Aseer region, Saudi Arabia. One hundred suspected PCP cases and 100 healthy controls were included in the study. Basic clinical manifestations, radiological findings, microbiological and immunological findings were extracted from the hospital records from January 2019 to August 2019, Pneumocystis detection was done by immune-fluorescent staining (IFAT, Gomorimethanamine silver staining (GMSS), Giemsa staining, Toluidine blue O (TBO), and Pneumocystis RT-PCR.Results: Increased more than 5 fold, 3 fold, 4 fold, and 7 fold of IL-2, IL-4, IL-10, and IL-13 mRNA expression were observed in PCP cases compared to controls. Higher expression of IL-2 mRNA was connected with crept, wheezing and chest X-ray findings like central perihilar infiltrate, patchy infiltrate, consolidation, hilar lymphadenopathy, pneumothorax, pleural effusion which showed higher expression compared to counterpart (p< 0.0001). Higher expression of IL-4 mRNA was found to be significantly associated with weight loss (p=0.002), dyspnea (p=0.003), crept (p=0.01), and chest X-ray findings (p< 0.0001). Significantly increased expression of IL-10 mRNA was observed to be associated with weight loss, dyspnea, night sweats, wheezing, and different findings of chest X-ray compared to their counterparts, whereas, IL-13 mRNA was observed in cases with fever. Suspected cases of PCP confirmed positive by IFTA with higher IL-2, IL-4, and IL-10 mRNA expression compared to negative cases. RT-PCR confirmed PCP cases had significantly higher expression of IL-2, IL-4, and IL-10 as well as IL-13 mRNA compared to negative cases. Positive detected cases by GMSS showed higher IL-2, IL-10 mRNA expression, while Giemsa showed only higher IL-4 mRNA expression compared to negative cases.Conclusion: Confirmed cases of P. jirovecii showed higher IL-2, IL-4, IL-10, and IL-13 mRNA expression comparatively to negative cases. Increased expression of cytokines may be indicative of infection severity and could help in patients' management. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the role of endometriosis leading to infertility in working females. Data Source: Data was collected and screened from Jinnah Hospital Lahore. Design and Study: Comparative cross sectional study was performed. Setting: Study was carried out in the Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore. Period: Present study was carried out over a period of two years from 14-11-2014 to 15-11-2016. Material and Methods: Hundred (n=100) patients of endometriosis and hundred (n=100) controls were added in the current study. Subjects were analyzed for the levels of MDA, SOD, CAT, GSH, ILs, MMPs, Vit-D, PGE-2, Estradiol, COX-2 and various hormones with the help of their respective spectrophotometric and kit protocols. Results: Levels of MDA, IL-8, MMP-2, TNF-a and Estradiol were significantly higherin patients of endometriosis (2.99±0.16 nmol/ml, 19.65±3.26 pg/ml, 563.23±48.2 ng/ml, 31.29±4.25 pg/ml and 47.16±4.28 pg/ml) vs. healthy females (0.88±0.089 nmol/ml, 10.26±1.99pg/ml, 299.35±54.4 ng/ml, 21.26±3.26pg/ml and 22.28±4.16pg/ml), whereas levels of SOD, CAT and GSH remained decreased significantly in patients infected by endometriosis (652.23±42.6, 1226.06±108.4 and 6.28±0.42 respectively). Levels of testosterone and 17ß-HSD-II were also significantly decreased females with endometriosis (15.23±1.99 ng/dL and 0.12±0.04 pg/ml respectively). Conclusion: The current study indicates role of oxidative stress and vitamin-D in females with endometriosis. Lower levels of vitamin-D and increased oxidative stress is responsible for release of induced factors i.e., PGE-2 and COX-2. These factors play their role in activation of signaling cascades involved in progression of endometriosis. Hence, vitamin-D and antioxidant supplementation may have a beneficial role in the disease management. [ABSTRACT FROM AUTHOR]

Emerging shreds of evidence suggest that tumor-associated macrophages (TAMs) modulate various hallmarks of cancer during tumor progression. Tumor microenvironment (TME) prime TAMs to execute important roles in cancer development and progression, including angiogenesis, matrix metalloproteinases (MMPs) secretion, and extracellular matrix (ECM) disruption. MicroRNAs (miRNAs) are critical epigenetic regulators, which modulate various functions in diverse types of cells, including macrophages associated with TME. In this review article, we provide an update on miRNAs regulating differentiation, maturation, activation, polarization, and recruitment of macrophages in the TME. Furthermore, extracellular miRNAs are secreted from cancerous cells, which control macrophages phenotypic plasticity to support tumor growth. In return, TAMs also secrete various miRNAs that regulate tumor growth. Herein, we also describe the recent updates on the molecular connection between tumor cells and macrophages. A better understanding of the interaction between miRNAs and TAMs will provide new pharmacological targets to combat cancer.

Highlights: [•] Redox-related transcription factor upregulation characterizes inflammation-related cancer. [•] NADPH oxidase-dependent ROS are associated with inflammation and tumor promotion. [•] Interdicting ROS-mediated inflammation is a novel cancer prevention strategy. [Copyright &y& Elsevier]

Abstract: Obesity is the cause of a large proportion of breast cancer incidences and mortality in post-menopausal women. In obese people, elevated levels of various growth factors such as insulin and insulin-like growth factors (IGFs) are found. Elevated insulin level leads to increased secretion of estrogen by binding to the circulating sex hormone binding globulin (SHBG). The increased estrogen-mediated downstream signaling favors breast carcinogenesis. Obesity leads to altered expression profiles of various adipokines and cytokines including leptin, adiponectin, IL-6, TNF-α and IL-1β. The increased levels of leptin and decreased adiponectin secretion are directly associated with breast cancer development. Increased levels of pro-inflammatory cytokines within the tumor microenvironment promote tumor development. Efficacy of available breast cancer drugs against obesity-associated breast cancer is yet to be confirmed. In this review, we will discuss different adipokine- and cytokine-mediated molecular signaling pathways involved in obesity-associated breast cancer, available therapeutic strategies and potential therapeutic targets for obesity-associated breast cancer. [Copyright &y& Elsevier]

Highlights: [•] Candida parapsilosis secrete two aspartic proteases which cleave human kininogens. [•] These proteases release two kinins, Met-Lys-bradykinin and Leu-Met-Lys-bradykinin. [•] Met-Lys-bradykinin and Leu-Met-Lys-bradykinin interact with kinin receptors B2. [•] These kinins stimulate endothelial cells to the secretion of interleukins 1β and 6. [•] In plasma, these kinins are converted into bradykinin and its des-Arg derivative. [ABSTRACT FROM AUTHOR]

Abstract: Airway hyperreactivity (AHR) is a major feature of asthmatic and inflammatory airways. Cigarette smoke exposure, and bacterial and viral infections are well-known environmental risk factors for AHR, but knowledge about the underlying molecular mechanisms on how these risk factors lead to the development of AHR is limited. Activation of intracellular mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) and their related signal pathways including protein kinase C (PKC), phosphoinositide 3-kinase (PI3K) and protein kinase A (PKA) signaling pathways may result in airway kinin receptor upregulation, which is suggested to play an important role in the development of AHR. Environmental risk factors trigger the production of pro-inflammatory mediators such as tumor necrosis factor-α (TNF-α) and interleukins (ILs) that activate intracellular MAPK- and NF-κB-dependent inflammatory pathways, which subsequently lead to AHR via kinin receptor upregulation. Blockage of intracellular MAPK/NF-κB signaling prevents kinin B1 and B2 receptor expression in the airways, resulting in a decrease in the response to bradykinin (kinin B2 receptor agonist) and des-Arg9-bradykinin (kinin B1 receptor agonist). This suggests that MAPK- and NF-κB-dependent kinin receptor upregulation can provide a novel option for treatment of AHR in asthmatic as well as in other inflammatory airway diseases. [Copyright &y& Elsevier]

Neuroinflammation is a characteristic of pathologically affected tissue in several neurodegenerative disorders. These changes are particularly observed in affected brain areas of Alzheimer''s disease (AD) cases. They include an accumulation of large numbers of activated microglia and astrocytes as well as small numbers of T-cells, mostly adhering to postcapillary venules. Accompanying biochemical alterations include the appearance or up-regulation of numerous molecules characteristic of inflammation and free radical attack. Particularly important may be the complement proteins, acute phase reactants and inflammatory cytokines. These brain phenomena combined with epidemiological evidence of a protective effect of antiinflammatory agents suggest that such agents may have a role to play in treating the disease. [Copyright &y& Elsevier]

Emerging shreds of evidence suggest that tumor-associated macrophages (TAMs) modulate various hallmarks of cancer during tumor progression. Tumor microenvironment (TME) prime TAMs to execute important roles in cancer development and progression, including angiogenesis, matrix metalloproteinases (MMPs) secretion, and extracellular matrix (ECM) disruption. MicroRNAs (miRNAs) are critical epigenetic regulators, which modulate various functions in diverse types of cells, including macrophages associated with TME. In this review article, we provide an update on miRNAs regulating differentiation, maturation, activation, polarization, and recruitment of macrophages in the TME. Furthermore, extracellular miRNAs are secreted from cancerous cells, which control macrophages phenotypic plasticity to support tumor growth. In return, TAMs also secrete various miRNAs that regulate tumor growth. Herein, we also describe the recent updates on the molecular connection between tumor cells and macrophages. A better understanding of the interaction between miRNAs and TAMs will provide new pharmacological targets to combat cancer. [ABSTRACT FROM AUTHOR]

IL levels were correlated with the mRNA levels of HMGB1/TLR-4 from allergic rhinitis patients with the analysis of Spearman correlation. • HMGB1 and TLR-4 were upregulated in AR patients, associating with nasal lavage ILs in AR patients. • TLR4 was associated with HMGB1 in nasal brushing samples from AR patients. • HMGB1/TLR4 pathway was associated with nasal lavage ILs in AR patients. High mobility group box 1 (HMGB1) acts as an inflammatory mediator initiator, and has shown to increase in nasal secretions of allergic rhinitis (AR) patients. The purpose of the present study was to investigate the association of HMGB1 and its receptor, toll-like receptor (TLR) 4 with proinflammatory interleukins in AR patients. The interleukin (IL) −4, −5, −13, −17A, −10 in nasal lavage fluid and the serum IgE were examined with enzyme-linked immunosorbent assay (ELISA) in 125 AR patients or 87 healthy subjects (as control). The mRNA levels of HMGB1, receptor for advanced glycation end products (RAGE) and TLR 2, 3 and 4 were examined in these participants with real-time quantitative PCR (RT-qPCR) method. Spearman rank correlation was adopted to analyze the relationship between any two factors of clinical characteristics and laboratory-examined biomarkers. IL-4, −5, −13 and −17A were significantly higher, whereas IL-10 was markedly lower in the nasal lavage fluid samples from AR patients, compared with the control subjects. High expression of HMGB1, TLR2 and TLR4 were observed in the nasal brushing samples from these AR patients, whereas there was no significant difference for the mRNA levels of TLR3 and RAGE. Besides, HMGB1/TLR4 mRNA levels correlated positively with IL-4, −5, −13 and −17A, whereas negatively with IL-10. A linear regression of HMGB1/TLR4 was also found positively with IL-4, −5 (only for TLR4), −13 or −17A, whereas negatively with IL-10. High mRNA levels of HMGB1 and TLR4 were found in the nasal brushing samples in AR patients, correlating positively with IL-4, −5, −13 or −17A, wheareas negatively with IL-10. HMGB1/TLR4 signaling pathway might be well responsive targets as immunotherapy for allergic rhinitis. [ABSTRACT FROM AUTHOR]

Asthma is a complex, heterogeneous, airway inflammatory disorder broadly classified into atopic (IgE mediated) and non-atopic asthma. Monoclonal Antibodies (MAbs) and small chemical Protein- Protein Interaction Modulators (PPIMs) are targeted against interleukins (ILs), which play a critical role in asthma. Many MAbs are targeted against ILs and IgE. Anti IgE MAb (Omalizumab) and Anti IL- 5 MAbs (Mepolizumab, Reslizumab) have only been approved by FDA. Most of the MAbs including Tracolizumab, Lebrikizumab, Anrukinzumab (Anti IL-13 MAb), and Brodalumab (Anti IL-17 MAb) are in different phases of clinical trials. Pascolizumab (Anti IL-4 MAb), however, has failed. These MAbs are expensive and may render adverse immune response. Thus, small chemical modulators targeting ILs and their receptors (IL-Rs) are being exploited computationally and further validated experimentally. The complex ILs and IL-Rs available in PDB are best suited for these types of studies. A large number of small chemical modulators against Protein-Protein Interactions (PPIs) have been compiled in a few databases like TIMBAL, 2P2I DB and IPPIDB. Small chemical libraries are used for virtual screening to find novel modulators targeting IL-R binding interface on IL. Molecular dynamic simulations have been further used for disruption mechanism and kinetic studies. IL-2/IL-2R was targeted with clinically tested small molecule modulators like SP4206, and IL-2 levels were known to increase in non-atopic asthma. In the absence of experimentally known modulators against atopic asthma, computational tools are being explored. For example, IL-33 is a target for atopic asthma where IL-33 and its receptor complex structure is available in PDB. In summary, small chemical modulators against ILs are a complementary approach to MAbs and computational tools have been used for identifying these modulators for asthma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)