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The cytokines IFN-γ, interleukin IL-1β, and TNF-α each up regulate the expression of major histocompatibility complex (MHC) and are therefore considered as inflammatory markers. The present study aimed to measure the serum levels of IFN-γ, interleukin IL-1β, and TNF-α in mice after induction of diabetes with streptozotocin and to correlate their levels to lipid and glycaemic profiles. The study included 40 Swiss Albino mice (20 males and 20 females), half of each male and female groups were made diabetic by intraperitoneal injection of streptozotocin. After 48 hours, the serum levels of INF-γ, IL1-β as well as TNF-α were measured with ELISA and their levels were correlated to lipid and glycaemic profiles. The levels of the cytokines, IFN-γ, IL1-β and TNF-α were measured and correlated to lipid profile, blood glucose and insulin. The serum levels of the three studied cytokines, IFN-γ, IL 1-β and TNF-α were statistically significantly higher among diabetic mice compared to the control group. Diabetic male mice (M-STZ mice) group showed significantly higher lipid profile compared to the control group (M-control). Cholesterol level was significantly higher among female control (F-control) compared to the M-control group. Cholesterol level was significantly higher among diabetic female mice (F-STZ mice) compared to the F-Control group. Regarding IFN-γ, IL 1-β and TNF-α levels, there were significant linear correlations with the glycemic profile (Glucose, insulin) reflected as positive correlation with blood glucose level and negative correlation with insulin level.

The hepatic endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) are mixed-function oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance. P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic turnover. Such P450 proteolytic turnover occurs through a process known as ER-associated degradation (ERAD) that involves ubiquitin-dependent proteasomal degradation (UPD) and/or autophagic-lysosomal degradation (ALD). Herein, on the basis of available literature reports and our own recent findings of in vitro as well as in vivo experimental studies, we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical relevance. We specifically (i) describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibody pathogenesis in drug-induced acute hypersensitivity reactions and liver injury, or viral hepatitis; (ii) discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates; and (iii) detail the pathophysiological consequences of disrupted P450 ERAD, contributing to non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) under certain synergistic cellular conditions., Graphical abstract In this article, we discuss the physiological, therapeutic and pathophysiological relevance of cytochrome P450 protein degradation. Employing mice with genetic ablation of CHIP and gp78/AMFR E3 ubiquitin-ligases that stabilize hepatic CYP2E1, we document why this stabilization not always leads to non-alcoholic fatty liver disease: It requires concomitantly enhanced hepatic lipogenesis.Image 1

Background Platelet-rich plasma (PRP) as well as other platelet-derived products have been used as a potential disease-modifying treatment for musculoskeletal diseases, such as osteoarthritis (OA). The restorative properties of such products rely mainly on the high concentrations of growth factors, demonstrating encouraging results experimentally and clinically. Yet, the autologous blood-derived nature of the PRP product lead to limitations that precludes it’s widespread use. The main limitations for PRP use are; product variability, the need for minimum laboratory settings in most cases, and the need for storage at low temperatures to preserve its properties. Based on these limitations, the objective of this study was to investigate an allogeneic off-the-shelf platelet lysate (PL) in cartilage exposed to interleukin 1β (IL-1β). For this purpose, blood and cartilage were harvested from eight skeletally mature and healthy horses. Blood was processed into PL aliquots and divided into three groups (Frozen, Freeze-dried and Filtered freeze-dried), used in autologous and allogeneic conditions and in three different concentrations (1.5, 3 and 6-fold). Different PL preparations were then applied in cartilage culture with interleukin-1 beta and cultured for 10 days. Cartilage and media samples were collected and analyzed for total GAG and 35SO4-labeled GAG content. Results No significant differences between the controls and PL groups in cartilage and media were demonstrated. The effects of PL on cartilage matrix were concentration dependent and intermediate concentrations (3-fold) in PL showed increased 35SO4-labelled GAG in cartilage. Conclusion In conclusion, the allogeneic freeze-dried PL presented equivalent effects compared to frozen autologous PL. Intermediate platelet concentration on average demonstrated improved results, demonstrating less GAG loss compared to other concentrations.

Chronic obstructive pulmonary disease (COPD), the leading cause of mortality and morbidity worldwide, is characterized by abnormal activation of inflammatory cells. The increased pro-inflammatory cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1β), further amplify the inflammation. We evaluated the dose response relationship of IL-1β and TNF-α levels and severity of airflow limitation, and differential responses in IL-1β and TNF-α between biomass COPD (BMS-COPD) and tobacco smoke COPD (TS-COPD) using a case control design in 160 subjects. Patients with COPD had higher serum levels of both IL-1β and TNF-α compared to healthy controls. A large difference in TNF-α was observed between TS-COPD and BMS-COPD, where TS-COPD patients had much higher levels. Serum IL-1β levels were higher in BMS-COPD. Levels of IL-1β correlated better with severity of airflow limitation than TNF-α levels. Both TNF-α and IL-1β levels had a negative linear relationship with Forced Expiratory Volume in 1st second (FEV1) and six-minute walk distance. The correlations were stronger with FEV1 than six-minute walk distance. The correlations of TNF-α and IL-1β with St George Respiratory Questionnaire (SGRQ) scores and body mass index (BMI) were not significant. In conclusion, the levels of pro-inflammatory cytokines TNF-α and IL-1β are differently elevated in TS-COPD and BMS-COPD, respectively.

Aim: We aimed to evaluate the correlation between the polymorphism of the interleukin 1-Beta (IL1-β, +3954 C>T) and tooth movement, in a group of Colombian patients undergoing surgically accelerated orthodontic tooth movement. Methods: The study was nested to a controlled clinical trial. Blood samples were taken from 11 women and 29 healthy Colombian male volunteers between 18 and 40 years old, after 1 year of starting orthodontic treatment. The patients presented malocclusion class I, with grade II or III. To detect the genetic polymorphism of the nucleotide +3954 C to T in the IL-1β gene, we used a real-time PCR assay. Results: Eleven individuals presented the allele 2 (T) heterozygous with the allele 1 (T/C) and 19 individuals were homozygous for the allele 1 (C/C). When analyzing the presence of the SNP, no significant differences were found in any of the variables. The best treatment was reflected in Group 3 (selective upper and lower alveolar decortication and 3D collagen matrix) and Group 4 (only selective alveolar decortication in the upper arch, with 3D collagen matrix), with 27% and 35% more speed respectively than in the control group. Conclusions: Our analyses indicated that a reduction in the total treatment time can be mostly potentiated by using decortication and collagen matrices and not for the presence of the allele 2 in the IL-1β. Nevertheless, it is important that further studies investigate if the polymorphism could be associated with the speed of tooth movement and analyze the baseline protein levels. Resumen Objetivo: Evaluar la correlación entre el polimorfismo de la interleucina 1-Beta (IL1-β, +3954 C> T) y el movimiento de los dientes, en un grupo de pacientes colombianos sometidos a un movimiento dental ortodóncico acelerado quirúrgicamente. Métodos: Este fue un estudio secundario derivado de un ensayo clínico aleatorio controlado. Se tomaron muestras de sangre de 11 mujeres y 29 voluntarios varones colombianos sanos entre 18 y 40 años, después de 1 año de comenzar el tratamiento de ortodoncia. Los pacientes presentaron maloclusión clase I, con grado II o III. Para detectar el polimorfismo genético del nucleótido +3954 C a T en el gen IL-1β, se usó un ensayo de PCR en tiempo real. Resultados: 11 individuos presentaron el alelo 2 (T) heterocigoto con el alelo 1 (T / C) y 19 individuos fueron homocigotos para el alelo 1 (C / C). Al analizar la presencia del SNP, no se encontraron diferencias significativas en ninguna de las variables. El mejor tratamiento se reflejó en el Grupo 3 (decorticación alveolar superior e inferior selectiva y matriz de colágeno 3D) y el Grupo 4 (solo decorticación alveolar selectiva en el arco superior, con matriz de colágeno 3D), con un 27% y un 35% más de velocidad, respectivamente, que en el grupo de control. Conclusiones: Los análisis indicaron que una reducción en el tiempo total de tratamiento puede potenciarse principalmente mediante el uso de decorticación y matrices de colágeno y no por la presencia del alelo 2 en la IL-1β. Sin embargo, es importante que otros estudios investiguen si el polimorfismo podría estar asociado con la velocidad del movimiento de los dientes y analizar los niveles de proteína de referencia.

Background: The clinical outcome of patients affected by dilated cardiomyopathy (DCM) is heterogeneous, since its pathophysiology is only partially understood. Interleukin 1&beta, levels could predict the mortality and necessity of cardiac transplantation of DCM patients. Objective: To investigate mechanisms triggering sterile inflammation in dilated cardiomyopathy (DCM). Methods: Hearts explanted from 62 DCM patients were compared with 30 controls, employing immunohistochemistry, cellular and molecular biology, as well as metabolomics studies. Results: Although misfolded protein accumulation and aggresome formation characterize DCM hearts, aggresomes failed to trigger the autophagy lysosomal pathway (ALP), with consequent accumulation of both p62SQSTM1 and dysfunctional mitochondria. In line, DCM hearts are characterized by accumulation of lipoperoxidation products and activation of both redox responsive pathways and inflammasome. Consistently with the fact that mTOR signaling may impair ALP, we observed, an increase in DCM activation, together with a reduction in the nuclear localization of Transcription Factor EB -TFEB- (a master regulator of lysosomal biogenesis). These alterations were coupled with metabolomic alterations, including accumulation of branched chain amino acids (BCAAs), known mTOR activators. Consistently, reduced levels of PP2Cm, a phosphatase that regulates the key catabolic step of BCAAs, coupled with increased levels of miR-22, a regulator of PP2Cm levels that triggers senescence, characterize DCM hearts. The same molecular defects were present in clinically relevant cells isolated from DCM hearts, but they could be reverted by downregulating miR-22. Conclusion: We identified, in human DCM, a complex series of events whose key players are miR-22, PP2Cm, BCAA, mTOR, and ALP, linking loss of proteostasis with inflammasome activation. These potential therapeutic targets deserve to be further investigated.

Background Biochemical markers including interleukins (ILs) has been proposed for early diagnosis of asphyxia Objective This study has aimed to systematically review the significance of IL measurements in the diagnosis of perinatal asphyxia. Materials and Methods PubMed, Cochrane Library, Web of Science, Embase, and Scopus databases before 2017 were searched for the following keywords: asphyxia, neonatal, interleukin, and diagnosis. A total of 13 out of 300 searched papers were finally selected for evaluation. Interleukins under study were IL6 and interleukin 1 β (IL-1 β ). Interleukins had been measured in 10 studies by serum samples, 2 studies by samples of Cerebro Spinal Fluid (CSF), and 1 study by sample of umbilical cord blood. The inclusion criteria were: studies on neonates, with adequate information from the test results and studies using markers other than ILs to detect asphyxia; however, studies with only abstracts available were excluded. Results Research on the issue suggests that IL6 > 41 Pg/dl has the sensitivity of 84.88% and the specificity of 85.43%, whereas IL-1 β > 4.7 Pg/dl has the sensitivity of 78% and specificity of 83% in the diagnosis of neonatal asphyxia. Among diagnostic ILs for neonatal asphyxia, combination of IL6 and IL-1 β had the highest sensitivity, that is, 92.9%. Conclusion IL6 and IL-1 β of serum samples were used in the early diagnosis of perinatal asphyxia and are useful predictors for the outcomes of perinatal asphyxia and its intensity. In addition, simultaneous evaluation of IL-1 β and IL6 can improve the sensitivity of the early diagnosis of perinatal asphyxia.

Objectives It is unknown whether a cytokine signature may help the identification of subgroup of patient who would respond to personalized treatment. As interleukin-1 beta (Il-1β) seems to play a major role in mood disorder, a systematic review and meta-analysis of its potential role in major depressive disorder (MDD) was carried out. Methods A systematic search was performed to identify appropriate MDD vs. control studies pertaining to Il-1β. Methodological quality and possible moderators were also assessed. Results A total of 1922 studies were identified, and 53 articles were selected. Results showed an association between increased blood IL-1β and MDD in high-quality studies only. No association with age was found. No IL-1β gene-related polymorphisms has been associated with MDD. No effect of antidepressant on IL-1β level has been found, although the antidepressants investigated were various. Qualitative analyses indicate that MDD coupled to a history of childhood trauma may be a subgroup for IL-1β -targeted therapies. No difference in studies utilizing a stimulation method has been identified to date. Conclusions The present work has confirmed IL-1β as a biological marker of interest for innovative MDD treatments. However, further studies are needed to clarify the patients with MDD who may benefit from these therapies.

Chronic Suppurative Otitis Media (CSOM) is a common public health problem worldwide and a major cause of hearing impairment. It is also one of the neglected disease especially in developing countries. Cytokines are a group of glycoproteins that play a role in strengthening the immune and inflammatory reactions in various diseases, including inflammation of the middle ear. Some of the important inflammatory mediators found in middle ear fluids are Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β). Cytokines are thought to play a role in the ongoing inflammatory regulation. The aim of this study was to compare the expression of TNF-α and IL-1β in tubotympanic CSOM and in healthy control group. The mean of TNF-α serum level in tubotympanic CSOM was 0,553±1,59 pg/ ml, and 0,587±2,13 pg/ ml in control group. There was no statistically different of TNF-α between two groups (P > 0,05). Mean of IL-1β serum level in the tubotympanic CSOM and control group were 0,633±0,92 and 0,302±0,48, respectively. Although IL-1β levels were higher in the patient group, the difference was not statistically significant (P > 0,05).

In orthodontic treatment remodeling of periodontal space is concomitant with the movement of teeth. Matrix metalloproteinase-8 and interleukin-1β are key markers of the initial tissue reaction in the processes of remodeling. The gingival fluid is the medium where changes in the profile and levels of these mediators occur. The aim of this study was to investigate the levels of matrix metalloproteinase-8 and interleukin-1β in gingival fluid samples during the first 3 months of orthodontic treatment with fixed appliances in children. Materials and methods: Twelve children receiving brackets treatment were included in the study; 48 samples of gingival fluid collected from one representative tooth of these children were measured once before placing the brackets, then at 24 hours, at 1 week, and at 3 months. We measured the amount of gingival fluid and the levels of matrix metalloproteinase-8 and interleukin-1β. Filter paper strips were used to collect gingival fluid. After eluting them we made a quantitative analysis of the biomarkers, matrix metalloproteinase-8 and interleukin-1β, using the solid-phase enzyme immunoassay (ELISA). The results showed a slight drop in the levels of both markers compared with baseline values and an increase at three months of orthodontic treatment. A similar tendency was observed in the flow of gingival fluid. Conclusion: Quantitative analysis of matrix metalloproteinase-8 and interleukin-1β in gingival fluid samples is potentially a non-invasive method by which orthodontists can get information about the remodeling processes in the periodontium during orthodontic treatment thus controlling and limiting them within physiological boundaries.

β were measured. The results show that serum concentration of testosterone was significantly higher in non stimulated cases. Also, the serum and follicular fluid concentrations of interleukin 6 and interleukin 1 β β β β in stimulated cases were significantly higher than non stimulated group. There was an important negative correlation between the level of testosterone in patient's serum and IL-6 and IL-1β levels of follicular fluid. In conclusion, according to these results, it seems that the levels of testosterone and IL-6 and IL-1β in patient's serum and follicular fluid are a good factor for prediction of maturity of oocytes.

The present study was performed to investigate the modulatory role of certain interleukin (IL)-1β in nociception with a nociceptive jaw opening reflex and an orofacial formalin test in freely moving rats. In an acute pain model, 10 pg, 100 pg and 1 ng IL-1β injected intracisternally did not change the digastric eletromyogram (dEMG). However, 10 ng IL-1β suppressed dEMG to 76±8 % of control values. In an inflammatory pain model, 10 pg IL-1β injected intracisternally did not change formalin-induced noxious behavioral responses. However, 100 pg IL-1β increased formalin-induced noxious behavioral responses. At higher dose of 10 ng IL-1β, it did not increase formalin-induced behavioral responses. Pretreatment with IL-1 receptor antagonist abolished hyperalgesic response of 100 pg IL-1β. These results suggest that the intracisternal injection of IL-1β modulate the transmission of nociceptive information in the orofacial area. The hypo/hyper-algesic responses of central cytokines seem to depend on the pain model or dose related manner and the hyperalgesic action seems to be mediated by IL-1 receptor.

Background Osteoarthritis (OA) is an inflammatory disease of synovial joints involving the loss and degeneration of articular cartilage. The gold standard for evaluating cartilage loss in OA is the measurement of joint space width on standard radiographs. However, in most cases the diagnosis is made well after the onset of the disease, when the symptoms are well established. Identification of early biomarkers of OA can facilitate earlier diagnosis, improve disease monitoring and predict responses to therapeutic interventions. Methods This study describes the bioinformatic analysis of data generated from high throughput proteomics for identification of potential biomarkers of OA. The mass spectrometry data was generated using a canine explant model of articular cartilage treated with the pro-inflammatory cytokine interleukin 1 β (IL-1β). The bioinformatics analysis involved the application of machine learning and network analysis to the proteomic mass spectrometry data. A rule based machine learning technique, BioHEL, was used to create a model that classified the samples into their relevant treatment groups by identifying those proteins that separated samples into their respective groups. The proteins identified were considered to be potential biomarkers. Protein networks were also generated; from these networks, proteins pivotal to the classification were identified. Results BioHEL correctly classified eighteen out of twenty-three samples, giving a classification accuracy of 78.3% for the dataset. The dataset included the four classes of control, IL-1β, carprofen, and IL-1β and carprofen together. This exceeded the other machine learners that were used for a comparison, on the same dataset, with the exception of another rule-based method, JRip, which performed equally well. The proteins that were most frequently used in rules generated by BioHEL were found to include a number of relevant proteins including matrix metalloproteinase 3, interleukin 8 and matrix gla protein. Conclusions Using this protocol, combining an in vitro model of OA with bioinformatics analysis, a number of relevant extracellular matrix proteins were identified, thereby supporting the application of these bioinformatics tools for analysis of proteomic data from in vitro models of cartilage degradation.

Airway smooth muscle may be an important cellular source of proinflammatory mediators and cytokines and may participate directly in airway inflammation. In this study we have examined whether airway smooth muscle cells could contribute to mechanisms of eosinophil accumulation by prolonging their survival. To investigate this possibility, conditioned medium from human airway smooth muscle cells stimulated with interleukin (IL)-1beta was examined on the in vitro survival of highly purified human peripheral blood eosinophils. After 7 d, when cultured in control medium, less than 1 +/- 0.2% of the initial eosinophil population remained viable. In contrast, culture in medium conditioned for 96 h by human airway smooth muscle cells stimulated with IL-1beta (1 pg-100 ng/ml) resulted in a concentration-dependent increase in eosinophil survival. (The concentration that produced 50% of this effect was 0.03 ng/ml IL-1beta.) Maximum eosinophil survival occurred at 1 to 3 ng/ml IL-1beta. This effect was also time-dependent and was readily detected in airway smooth muscle cell-conditioned medium after just 3 h of stimulation with IL-1beta (1 ng/ml). It continued to increase before reaching a plateau around 24 h, with no decrease in activity for up to 120 h of stimulation. Conditioned medium from unstimulated airway smooth muscle cells did not enhance eosinophil survival. The survival-enhancing activity was completely inhibited (the concentration that inhibited 50% [IC50] was 6.9 microg/ml) by a polyclonal goat antihuman antibody to granulocyte-macrophage colony stimulating factor (GM-CSF) (0.3-100 microg/ml), but antibodies (10-100 microg/ml) to IL-3 and IL-5, and a normal goat immunoglobulin G control had no effect on the eosinophil survival-enhancing activity. GM-CSF levels in culture medium from smooth muscle cells were markedly increased by IL-1beta and were maximum at 30 ng/ml (0.037 ng/ml/10(6) cells versus 3.561 ng/ml/10(6) cells, unstimulated versus 30 ng/ml IL-1beta). The IL-1 receptor antagonist inhibited both the production of GM-CSF (IC50 19. 1 ng/ml) and the eosinophil survival-enhancing (IC50 53.7 ng/ml) activity stimulated by IL-1beta. Release of GM-CSF elicited by IL-1beta was inhibited by dexamethasone but not by indomethacin. These data indicate that cultured human airway smooth muscle cells stimulated with IL-1beta support eosinophil survival through production of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation in the airways.

Cultured human monocytes have been incubated with powdered cubic [60] fullerene. No modification has been observed with [60] fullerene when compared with negative control (monocytes alone).

Very little is known about the role of interleukin-1β(IL-1β) and interleukin-18 (IL-18) in urticaria.Material and Methods. Serum levels of IL-1β, IL-1 receptor antagonist (IL-1RA), and IL-18 were measured in 56 children with urticaria and in 41 healthy subjects.Results. Serum IL-1βdid not differ between children with acute urticaria and controls. Children with single episode of urticaria had higher levels of IL-1RA and IL-18 than healthy subjects. In children with single episode of urticaria, level of IL-1RA correlated with C-reactive protein (CRP), D-dimer, and IL-1βlevels. In subjects with recurrence of urticaria IL-1RA was positively correlated with WBC and D-dimer levels. No correlation of cytokine levels and urticaria severity scores (UAS) in all children with urticaria was observed. In children with single episode of urticaria UAS correlated with CRP level. In the group with single episode of urticaria and in children with symptoms of upper respiratory infection, IL-1RA and IL-18 levels were higher than in controls. The former was higher than in noninfected children with urticaria. In conclusion, this preliminary study documents that serum IL-1RA and IL-18 levels are increased in some children with acute urticaria. However further studies are necessary to define a pathogenic role of IL-1β, IL-1RA, and IL-18 in urticaria.

Interleukin-1 is involved in host defense to infection and injury. In this work synthesis and secretion of IL-1 by cultured rat liver macrophages (Kupffer cells) in response to lipopolysaccharide were investigated. IL-1 was found only intracellularly as 31-kD (pro-IL-1 alpha) and 34-kD (pro-IL-1 beta) proteins. No mature 17-kD IL-1 alpha or IL-1 beta was detected in cell lysates or supernatants. Pulse-chase experiments showed that there was no release of IL-1 even after 24h, although pro-IL-1 continuously disappeared from the cells. Cultures were lysed by freezing-thawing. Pro-IL-1 beta was then found in the supernatants, but pro-IL-1 alpha was processed into several smaller fragments. A 17-kD protein could represent the mature IL-1 alpha. The results indicate that Kupffer cells are not able to secrete biologically active mature IL-1 proteins. By lysis of the cells. IL-1 is released. Pro-IL-1 alpha is processed, but pro-IL-1 beta seems to need further activation processes.

The ability of the intracerebroventricular (icv) injection of interleukin-1 beta (IL-1 beta) to alter plasma prolactin (PRL) levels in rats remains controversial, with reports of increases, decreases, or no changes in secretory rate. These discordant results may reflect, at least in part, the use of different doses of cytokines, as well as a gender specificity in the response of the brain circuits that control PRL release. In a first series of experiments, we investigated the effect of one acute icv injection of IL-1 beta to alter PRL secretion in intact male and female rats. Using this paradigm, we also determined the potential modulating role of secretagogues reportedly released by IL-1 beta, such as dopamine, corticosterone and progesterone. A second series of experiments involved the long-term (3-5 days) i.c.v. infusion of IL-1 beta to identify the influence of gender on the pattern of PRL release. The acute icv injection of IL-1 beta (5-50 ng) to intact adult males or females caused comparable and significant (p0.01) decreases in plasma PRL levels 1-5.5 h after treatment. At the 8 h time point PRL secretion started to increase in females exposed to the cytokine, while PRL values of males were comparable in vehicle- and IL-1-injected rats. In intact males, blockade of pituitary dopamine receptors with domperidone (3.5 mg/kg) did not reverse the inhibitory effect of the immune protein. In either gender, blockade of IL-1-induced corticosterone and adrenal progesterone release with CRF antibodies was also without effect on PRL secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural and functional similarities have been discovered between two mammalian proteins, Bcl-2 and interleukin 1 β -converting enzyme, and proteins encoded by nematode cell-death genes.

To study post-operative plasma concentrations of tumor necrosis factor alpha (TNF), interleukin-1 beta (IL-1) and interleukin-6 (IL-6) in infected and non-infected patients.Prospective controlled clinical study.The intensive care unit (ICU) of a university hospital.The study comprised 20 patients, 9 infected and 11 non-infected, consecutively admitted to the ICU after moderate or major surgery. Twelve healthy volunteers were used as controls.Leucocyte count, CRP and the plasma TNF, IL-1 and IL-6 concentrations were studied 24-48 h after the start of surgery. Axillary temperature, the duration of surgery, the number of packed red cells transfused, the APACHE II score and outcome were registered. Both infected and non-infected patients had higher plasma concentrations of IL-6 than the controls (p0.001 and p0.01 respectively). Patients with infection had a higher plasma IL-6 concentration than non-infected patients (p0.05). Similar analyses of plasma TNF concentrations revealed no differences between infected and non-infected patients. Plasma IL-1 was detected only occasionally. Non-survivors (n = 4) had higher plasma concentrations of TNF and IL-6 than survivors (p0.05 and p = 0.05 respectively). In non-infected patients a correlation between the number of units of packed red cells transfused and the plasma IL-6 concentration was observed (r = 0.73, p0.05).No specific plasma cytokine pattern for infected patients subjected to surgery was observed. The effect of surgery and infection on the plasma IL-6 concentration seemed to be additive. Transfusion of packed red cells appeared to elevate the post-operative plasma IL-6 concentration.

The resonance assignments of the human NLRP7 PYD domain have been determined based on triple-resonance experiments using uniformly [(13)C,(15)N]-labeled protein. This assignment is the first step towards the 3D structure determination of the NLRP7 PYD domain.

The effect of intratesticular administration of interleukin-1beta (IL-1beta) on steroidogenesis was studied in immature and adult rats. In 21-d-old animals local bilateral injection or unilateral administration of 0.1 microg/testis of IL-1beta to hemicastrates resulted in a significant increase in basal testosterone secretion in vitro and serum testosterone concentration one day posttreatment. Six days after treatment the cytokine induced opposite effect in animals with two testes in situ, i.e., it suppressed steroidogenesis. When IL-1beta was combined with hemi-castration, IL-1beta failed to alter the parameters studied. In adult animals subjected to bilateral treatment or to unilateral injection followed by hemicastration, IL-1beta in doses of 1.5 microg/testis or 15 microg/testis did not influence steroidogenesis and serum testosterone concentration. No change in serum LH and FSH concentration could be observed in any experimental group. The data suggest that the proinflammatory cytokine IL-1beta exerts a local action on testicular steroidogenesis, and the effect is age-dependent.