Cytokine Levels In Patients Research Articles

Perioperative cytokine profile during lung surgery predicts patients at risk for postoperative complications-A prospective, clinical study.

BackgroundPostoperative complications after lung surgery are frequent, having a detrimental effect on patients’ further course. Complications may lead to an increased length of hospital stay and cause additional costs. Several risk factors have been identified but it is still difficult to predict contemporary which patients are at risk. We hypothesized that patients who show an increased inflammatory response at the time of wound closure and 24 hours after surgery are at risk of postoperative complications within 30 days after surgery.MethodsPostoperative complications (pulmonary, cardiac, neurological and renal) of 96 patients scheduled for lung surgery at the Medical Center–University of Freiburg were analyzed in this prospective, clinical study. Blood samples for cytokine analysis (Interleukin (IL)-6, IL-8, IL-10, Tumor necrosis factor [TNF]-α, IL-1ß and IL12p70) were taken before surgery, at wound closure and 24 hours after surgery. Cytokine levels of patients with and without postoperative complications were analyzed by Receiver operating characteristic (ROC) curve analysis. To adjust the results according to existing covariates a multivariate logistic regression analysis was conducted.ResultsThe complication and non-complication group differed significantly according to nicotine dependency, Angiotensin-receptor-II blocker medication, rate of thoracotomy and preoperative lung function. The intraoperative hemodynamic parameters and therapy did not differ between the groups. Twenty-nine patients (30%) developed postoperative complications within 30 days after surgery. Plasma concentrations of IL-6, IL-10 and IL-8 at the time of wound closure and 24 hours after surgery were higher in the complication group. Multivariate regression analysis on postoperative complications revealed an Odds ratio of 56 for patients with IL-6 and IL-8 levels above the 3rd quartile measured on the first postoperative day.ConclusionsPerioperative detection of increased plasma concentrations of inflammatory cytokines in lung surgery may be used in addition to other clinical predictors to identify patients at risk for postoperative complications.Trial registrationGerman Clinical Trials Register 00006961.

Altered levels of cytokines in patients with irritable bowel syndrome are not correlated with fatigue

IntroductionA considerable number of patients with gastrointestinal complaints attributable to irritable bowel syndrome (IBS) have shown evidence of immune activation. Fatigue is also frequently reported by IBS patients and the condition is considered as a common comorbidity of IBS. Therefore, it is interesting to see whether these two conditions share the same pathophysiological mechanism.AimsTo investigate the potential role of cytokine profiles in patients with IBS and the relationship between cytokine profiles and fatigue.Materials and methodsThirty-eight patients with IBS (32 females, 6 males, age range 18–70 years) and 22 healthy individuals (control group) (17 females, 5 males, age range 24–42 years) were included. IBS was diagnosed according to Rome III criteria, and severity of IBS symptoms and fatigue were evaluated using the Irritable Bowel Syndrome-Severity Scoring System (IBS-SSS) and Fatigue Impact Scale (FIS), respectively. FIS scores of 25 or higher were defined as fatigue. Blood samples were also taken, and the Luminex® platform (Cytokine Human Ultrasensitive Magnetic 10-Plex Panel) was used for quantifying human cytokines’ profile (granulocyte-macrophage colony-stimulating factor, interferon-γ, interleukin [IL]-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, and tumor necrosis factor [TNF]-α) in serum.ResultsThe serum levels of IL-5, IL-6, IL-10, and TNF-α were significantly higher in patients with IBS compared to healthy controls (p=0.003, p=0.011, p=0.007, and p=0.02, respectively). Conversely, serum levels of cytokine IL-1β were significantly higher in the control group (p=0.03). The findings were consistent when comparing nonatopic patients with controls. Fatigue was demonstrated in 84.2% of the IBS patients. Scores of IBS-SSS were not significantly correlated with FIS scores (r=0.2, p=0.19), and they were not significantly different in patients with FIS scores >25 compared to patients with FIS scores <25 (p=0.11). None of the cytokine levels were significantly different in IBS patients with FIS scores >25 compared to IBS patients with FIS scores <25. Moreover, the cytokine levels in participants did not vary significantly between patients with diarrhea, constipation, or mixed bowel habits in multiple comparisons of patients.ConclusionsThe cytokines IL-5, IL-6, IL-10, and TNF-α may contribute to the development of IBS. However, serum levels of cytokines were not significantly different in IBS patients with fatigue compared with IBS patients without fatigue. Thus, the significance of cytokine levels may be less important than anticipated in search of common underlying mechanisms, and other factors should be explored in future studies.

Smoking, disease characteristics and serum cytokine levels in patients with primary Sj\xf6gren\u2019s syndrome

Smoking affects several disease processes. Epidemiological studies have previously found a negative association between primary Sjögren’s syndrome (pSS) and smoking. The aim of this study was to examine whether markers of disease activity and cytokine expression in pSS patients differ between ever and never smokers. Fifty-one consecutive pSS patients and 33 population controls were included in the study. Clinical and standard laboratory parameters were registered. Serum cytokines (IL-1β, IL-2, IL-3, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, IL-33, IFN-α, IFN-γ, TNF-α, EGF, BAFF, Fas-ligand, RANTES, TGF-β1) were assessed. A positive lip biopsy was less prevalent among ever smoking patients compared to never smokers (81 vs 100%; p = 0.03). However, except for TNF-α, which was higher in ever smokers, no differences in cytokine levels were found when comparing ever and never smoking pSS patients. Furthermore, no significant differences were found between ever and never smoking patients in the ESSDAI total score, IgG levels, or complement levels. However, IL-6, IL-12, IL-17 and IL-18 were significantly increased in pSS patients compared to controls. In this study, a negative association between ever smoking and positive lip biopsy was found, confirming previous reports. Expected differences in cytokine levels compared to controls were noted, but no major differences were found between ever and never smoking pSS patients. Taking into account the negative association between pSS diagnosis and smoking in epidemiological studies, possible explanations include a local effect of smoking on salivary glands rather than systemic effects by cigarette smoke.

Cytokine alterations in first-episode schizophrenia and bipolar disorder: relationships to brain structure and symptoms

BackgroundOver the past 30 years, evidence has been accumulating for an immunological component to schizophrenia etiology, including genetic links to the major histocompatibility complex, microglia activation, and dysregulated cytokine profiles. However, the degree of similarity in cytokine profiles for schizophrenia and bipolar disorder, as well as the relationship between cytokine levels and brain structure, is less well understood.MethodsTo address this, we recruited 69 first-episode schizophrenia-spectrum patients, 16 first-episode bipolar patients with psychotic features, and 53 healthy controls, from the UC Davis EDAPT clinic. Blood plasma was collected and analyzed for all participants with a subset of participants that also underwent structural MRI on a 1.5T GE scanner.ResultsPlasma levels of interleukin (IL)-1β, IL-2, IL-6, and interferon (IFN)-γ were elevated in schizophrenia patients compared to those in controls. Patients with bipolar disorder had elevated plasma IL-10 levels compared to controls, and the two patient groups did not differ significantly on any immunological measure. Percent whole-brain gray matter was inversely correlated with IFN-γ and IL-12 levels in patients with schizophrenia, with a trend relationship between IFN-γ and IL-12 and prefrontal cortical thickness. Furthermore, psychotic symptoms were positively related to IL-1β levels in individuals with schizophrenia.ConclusionsThese data suggest a partially overlapping pattern of elevated blood cytokine levels in patients with first-episode schizophrenia and bipolar disorder with psychotic features. Furthermore, our findings suggest that elevated pro-inflammatory cytokines may be particularly involved in schizophrenia etiology, given evidence of cytokine-related decreases in total gray matter.

Clinical Remission of Sight-Threatening Non-Infectious Uveitis Is Characterized by an Upregulation of Peripheral T-Regulatory Cell Polarized Towards T-bet and TIGIT.

Non-infectious uveitis can cause chronic relapsing and remitting ocular inflammation, which may require high dose systemic immunosuppression to prevent severe sight loss. It has been classically described as an autoimmune disease, mediated by pro-inflammatory Th1 and Th17 T-cell subsets. Studies suggest that natural immunosuppressive CD4+CD25+FoxP3+ T-regulatory cells (Tregs) are involved in resolution of inflammation and may be involved in the maintenance of clinical remission. To investigate whether there is a peripheral blood immunoregulatory phenotype associated with clinical remission of sight-threatening non-infectious uveitis by comparing peripheral blood levels of Treg, Th1, and Th17, and associated DNA methylation and cytokine levels in patients with active uveitic disease, control subjects and patients (with previously active disease) in clinical remission induced by immunosuppressive drugs. Isolated peripheral blood mononuclear cells (PBMC) from peripheral blood samples from prospectively recruited subjects were analyzed by flow cytometry for CD3, CD4, FoxP3, TIGIT, T-bet, and related orphan receptor γt. Epigenetic DNA methylation levels of FOXP3 Treg-specific demethylated region (TSDR), FOXP3 promoter, TBX21, RORC2, and TIGIT loci were determined in cryopreserved PBMC using a next-generation sequencing approach. Related cytokines were measured in blood sera. Functional suppressive capacity of Treg was assessed using T-cell proliferation assays. Fifty patients with uveitis (intermediate, posterior, and panuveitis) and 10 control subjects were recruited. The frequency of CD4+CD25+FoxP3+ Treg, TIGIT+ Treg, and T-bet+ Treg and the ratio of Treg to Th1 were significantly higher in remission patients compared with patients with active uveitic disease; and TIGIT+ Tregs were a significant predictor of clinical remission. Treg from patients in clinical remission demonstrated a high level of in vitro suppressive function compared with Treg from control subjects and from patients with untreated active disease. PBMC from patients in clinical remission had significantly lower methylation levels at the FOXP3 TSDR, FOXP3 promoter, and TIGIT loci and higher levels at RORC loci than those with active disease. Clinical remission was also associated with significantly higher serum levels of transforming growth factor β and IL-10, which positively correlated with Treg levels, and lower serum levels of IFNγ, IL-17A, and IL-22 compared with patients with active disease. Clinical remission of sight-threatening non-infectious uveitis has an immunoregulatory phenotype characterized by upregulation of peripheral Treg, polarized toward T-bet and TIGIT. These findings may assist with individualized therapy of uveitis, by informing whether drug therapy has induced phenotypically stable Treg associated with long-term clinical remission.

Elevated peripheral blood B lymphocytes and CD3+CD4-CD8- T lymphocytes in patients with non-small cell lung cancer: A preliminary study on peripheral immune profile.

It has been established that the tumor microenvironment (TME) has a crucial role in enabling tumors to evade from host immune responses. Previous studies demonstrated that tumor cells are not only able to reshape immune milieu at the tumor site, but also exert systemic effects, which has been demonstrated to be important for metastasis. At present, how the peripheral immune environment change in the tumor-bearing host is unclear. The present study identified a number of changes in the proportions of lymphocyte subpopulations and the levels of cytokines in patients with NSCLC, which may provide a preliminary profile of the immune environment in the peripheral blood of patients harboring a tumor. These findings expand on the present knowledge on how tumors can alter the immune system to benefit its growth and metastasis, which may provide a potential novel strategy for immunotherapy.

The impact of serum cytokines in the development of early allograft dysfunction in living donor liver transplantation.

Early allograft dysfunction (EAD) is considered a precursor to graft loss in liver transplantation. To date, the use of preoperative serum cytokine profiles to predict EAD development has not been systematically investigated in living donor liver transplantation (LDLT). Here, we investigated the association between preoperative serum cytokine profiles and EAD development in LDLT patients.Serum cytokine profiles collected preoperatively and on postoperative day 7 were retrospectively reviewed. The specific serum cytokines analyzed included interleukin (IL)-2, IL-6, IL-10, IL-12, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α. The cytokine levels of patients with EAD were compared with those of patients without EAD and the impact of cytokine levels on the occurrence of EAD was evaluated.Preoperatively, the serum levels of IL-6, 10, 17, and TNF-α were significantly higher in the EAD group than in the non-EAD group. In univariate logistic analysis, the preoperative levels of IL-6, IL-10, IL-17, IFN-γ, and TNF-α were potentially associated with EAD development. After multivariate logistic analysis, higher preoperative serum levels of IL-6 and 17 were significantly associated with EAD development. In addition, the incidence of EAD increased as the preoperative serum levels of IL-6 and IL-17 increased.Preoperative serum levels of IL-6 and IL-17 were significantly associated with EAD development in LDLT.

Modulation of high-density lipoprotein and cytokine IL-1β and IL-6 levels in patients with dengue

To assess High-Density Lipoprotein (HDL) and pro-inflammatory cytokine levels in patients with dengue classified according to the severity of the clinical presentation. A descriptive study was carried out with 70 individuals with dengue, classified as no alarm signs (DSSA), with signs of alarm (DCSA), and severe dengue (DG); 15 healthy donors were included as controls (CS). The serum levels of IL-1β and IL-6 were quantified through ELISA, and the HDL levels through serum by a colorimetric test. In addition, the platelet count and the hematocrit percentage were determined. Levels of IL-1β and IL-6 were found to be increased in patients with DENV vs. the healthy controls. Said increase was more evident in patients with dengue and in line with the severity of the clinical presentation. The HDL levels were found to be decreased in patients with dengue versus healthy controls. The correlation analysis showed statistically significant associations between HDL and the platelet number, as well as between the hematocrit percentage and the levels of IL-1β. The increased IL-1β and IL-6 and the decreased HDL levels in the most severe clinical stages suggest that both factors are involved in the development of the pathogenesis and severity. The correlations allow the observation of a potential association between HDL and platelet count, which allows us to provide an approach to the possible role of HDL in the pathogenesis of dengue, but it is still necessary to perform additional studies that will allow to state their importance in the course of the DENV infection.

Circulating cytokine levels are associated with symptoms of depression and anxiety among people with alcohol and drug use disorders

BackgroundPsychological distress is common among people with a substance abuse disorder in treatment. Identifying correlates of psychological distress may serve as points of intervention to improve substance abuse treatment outcomes. Immune function measured as cytokine levels have been associated with psychological distress, but this association remains unexplored among people with a substance abuse disorder in treatment. This study aimed to examine whether cytokine levels in patients treated for a substance use disorder were related to depression, anxiety, and overall psychological distress, and to observe these associations separately among people with a past year alcohol use disorder and those with a past year drug use disorder. MethodsWe collected cross-sectional data from 80 inpatients at five alcohol and substance abuse treatment centers in Norway. We determined alcohol and drug diagnoses, and assessed symptoms of depression, anxiety, and overall psychological distress. We tested blood samples for IL-1, IL-6, TNF-α, INF-γ, and IL-10. We used multivariate linear regressions to examine the associations between cytokine levels and psychological distress measures. ResultsAll cytokines were significantly and positively associated with depression score. INF-γ was significantly and negatively associated with anxiety, and IL-6 was significantly and positively associated psychological distress. Among people with only an alcohol use disorder, IL-6 was positively associated with depression and psychological distress scores, and IL-10 was negatively associated with anxiety score. Among people with only a drug use disorder, TNF-α was positively associated with depression score. ConclusionThe relationship between immune function and psychological distress is robust in the context of substance abuse, and further research is warranted.

RETRACTED ARTICLE: Preoperative versus postoperative ultrasound-guided rectus sheath block for improving pain, sleep quality and cytokine levels in patients with open midline incisions undergoing transabdominal gynecological surgery: a randomized-controlled trial

BackgroundNerve block is usually performed before surgery because it inhibits reflection of the skin incision and reduces the amount of intraoperative anesthetic used. We hypothesized that performing rectus sheath block (RSB) after surgery would result in a longer duration of the analgesic effects and have a subtle influence on sleep time after surgery but that it would not decrease the perioperative cytokine levels of patients undergoing gynecological surgery.MethodsA randomized, double-blinded, controlled trial was conducted from October 2015 to June 2016. Seventy-seven patients undergoing elective transabdominal gynecological surgery were randomly assigned to the following two groups: a general anesthesia group who received 0.5% ropivacaine hydrochloride RSB preoperatively and saline RSB postoperatively, and another group who received the opposite sequence. The objective of the trial was to evaluate the postoperative pain, sleep and changes in cytokine levels of patients during the postoperative 48 h.ResultsA total of 61 female patients (mean age: 50 years; range: 24–65 years) were included in the final study sample. There was no significant difference in the pain, consumption of oxycodone, or time to first administration of patient-controlled intravenous analgesia between the two groups. The postoperative sleep stages N2 and N3 were increased by 52.9 and 29.1 min per patient, respectively, in the preoperative RSB group compared with those in the postoperative group. The preoperative IL-6 concentration in the preoperative RSB group was lower than that in the same group at the end of surgery and 24 h postoperatively.ConclusionsWe concluded that preoperative RSB might preserve postoperative sleep by inhibiting the increase of IL-6 without shortening the analgesia time compared with postoperative RSB in female patients undergoing elective midline incision transabdominal gynecological surgery.Trial registrationClinicalTrials.gov, NCT02477098, registered on 15 June 2015.

Salivary Cytokine Levels in Lung Cancer with Distant and Regional Metastases

Optimization of methods for diagnostics and prediction of lung cancer, which occupies a leading position in the structure of oncological diseases, still remains an important task. In this study we have investigated the level of cytokines and acute-phase proteins in saliva of patients with lung cancer in dependence on the tumor size, and distant and regional metastasis. The case-control study included 121 patients, which were divided into 3 groups: the main group (patients with diagnosed lung cancer, n=70), the reference group (patients with non-malignant lung pathologies, n=12) and the control group (conditionally healthy individuals, n=39). All participants answered the questionnaire, underwent biochemical study of saliva and histological verification of the diagnosis. The content of IL-2 and IL-4 in saliva reduced in both lung cancer and inflammatory lung diseases, whereas the levels of IL-18, IL-8 and TNF-a decreasd in lung cancer and increased in non-malignant pathologies. Tumor progression was accompanied by an increase in the level of proinflammatory cytokines (IL-6, IL-8, IL-18, TNF-a), whereas the levels of IL-2, IL-4 and IL-10 decreased. Although saliva levels of C-reactive protein and tumor markers increased in lung cancer they did reach the level of statistical significance as compared with the reference group. Thus, with the only exception of IL-2 and IL-4, the saliva levels of cytokines in lung cancer patients insignificantly differ from the control group. However, the recognzied dynamics of the saliva cytokines level in patients with distant and regional metastasis opens the prospect of using these parameters for monitoring the treatment and controlling relapse occurrence.

Erythrocyte membrane fatty acid profile & serum cytokine levels in patients with non-alcoholic fatty liver disease.

Background & objectives:Fatty acids may affect the expression of genes, and this process is influenced by sex hormones. Cytokines are involved in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), so this study was aimed to assess the association of erythrocyte membrane fatty acids with three cytokines and markers of hepatic injury in NAFLD patients and to explore whether these associations were the same in both sexes.Methods:In this cross-sectional study, 62 consecutive patients (32 men and 30 women) with NAFLD during the study period. Tumour necrosis factor-α (TNF-α), interleukin 6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), aspartate aminotransferase and alanine aminotransferase were measured in a fasting serum sample, and Fibroscan was conducted for each individual. Gas chromatography was used to measure erythrocyte membrane fatty acids. Univariate and multiple linear regressions were used to analyze data.Results:In men, IL-6 had a significant (P <0.05) positive association with total ω-3 polyunsaturated fatty acids (PUFAs). In women, TNF-α had a significant positive association with total ω-3 (P <0.05) and ω-6 (P <0.01) PUFAs, IL-6 had a significant (P <0.05) positive association with total monounsaturated fatty acids and MCP-1 had a significant positive association with total trans-fatty acids (P <0.05). No significant associations were observed between erythrocyte membrane fatty acids and liver enzymes or Fibroscan report in both sexes. In this study, women were significantly older than men [51 (42.75-55) vs 35.5 (29-52), P <0.01], so the associations were adjusted for age and other confounders.Interpretation & conclusions:Erythrocyte membrane fatty acid profile was not associated with serum liver enzymes or Fibroscan reports in NAFLD patients, but it had significant associations with serum TNF-α, IL-6 and MCP-1 and these associations were probably sex dependent.

Features of cytokine production in different forms of Epstein-Barr virus infection

In article presented results of the study of basic levels of regulatory cytokines in patients with various forms of Epstein-Barr virus infection. Analysis of the dynamics of cytokine profile in patients with Epstein-Barr virus infection revealed the opposite changes studied synthesis of proinflammatory and anti-inflammatory cytokines, which was the basis for the establishment of the four types of immune response. The findings confirm the existence of cytokine imbalance with Epstein-Barr virus infection. The established types of immune responses indicate inadequate cell humoral reactivity in a long persistence of Epstein-Barr virus infection, which manifests a tendency to suppression of cell-mediated and humoral immune response enhancement mechanisms and displayed in the clinical and biochemical manifestations of the disease, and also leads to prolonged undulating course. The results of studies confirm the existence of cytokine imbalance in various forms of EBV infection. The established types of immune response indicate inadequate cellular-humoral reactivity of the organism under the conditions of long-term EBV persistence. This is manifested by a tendency to suppress cell-mediated and increased humoral mechanisms of the immune response and is displayed in the clinical and biochemical manifestations of the disease and leads to a prolonged wave-like course of the disease. Interesting and promising are studies aimed at the medical correction of identified disorders in established types of immune response in patients with HEVE and studying the effects of the latter on the outcomes of the disease, the development of complications and activity of the process, which will be the subject of our further study.

Distribution of circulating T follicular helper cell subsets is altered in immunoglobulin A vasculitis in children.

BackgroundImmunoglobulin A vasculitis (IgAV) is the most common vasculitis in children. Previously, we demonstrated that patients with IgAV show abnormal proliferation of cluster of differentiation (CD)4+C-X-C chemokine receptor type (CXCR)5+ follicular helper T (Tfh) cells. Here, we explored the status of Tfh cell subsets and plasma cytokine levels in patients with IgAV.MethodsCD4+CXCR5+CD45RA−, CD45RA-CXCR3+CCR6−, CD45RA−CXCR3−CCR6−, CD45RA−CXCR3−CCR6+, and CD45RA−CXCR3+CCR6+ Tfh cell fractions and plasma concentrations of interferon-γ, interleukin (IL)-4, and IL-17A were evaluated by flow cytometry and a flow cytometric bead array, respectively, in 30 patients with IgAV and 15 healthy controls (HCs).ResultsTfh2 and Tfh17 cell fractions were larger and the Tfh2+Tfh17/Tfh1 ratio and plasmaIL-4 and -17A levels were higher in patients with IgAV than in the HCs. Only Tfh1 cell counts were reduced in the abdominal subtype. The elevations in Tfh2 and Tfh17 cell counts and plasma IL-4 levels were abrogated by treatment. Tfh2 cell number was positively correlated with serum IgA and plasma IL-4 levels, but negatively correlated with the serum C4 concentration, while Tfh17 cell number was positively correlated with the serum IgA level and Tfh2 cell counts.ConclusionsAbnormally high numbers of Tfh2 and Tfh17 cells are linked to the occurrence and development of IgAV, but are not specific to the abdominal type. Only Tfh1 cells play a critical role in abdominal-type IgAV.

Serum Levels of IL-6, IL-8, TNF-α, and TGF-β in Chronic HBV-Infected Patients: Effect of Depression and Anxiety.

To assess the effects of depression and anxiety on serum cytokine levels in patients with chronic hepatitis B (CHB) infection. In this cross-sectional study, 60 healthy control individuals and 60 patients with CHB participated after filling out standard questionnaires. We examined their serum interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-α, and TGF-β levels using enzyme-linked immunosorbent assay (ELISA) techniques. In patients with CHB compared with healthy controls, serum levels of IL-8 were significantly increased, whereas IL-6 and TGF-β levels were significantly decreased. Serum levels of TGF-β were significantly decreased in the patients with CHB who had mild depression, compared with patients with CHB without depression and with moderate and severe depression. Downregulation of IL-8 and TGF-β, respectively, is a corresponding mechanism for induction of chronic inflammation in patients with CHB. Depression also seems to induce inflammation via downregulation of TGF-β in these patients.

Концентрации цитокинов в периферической крови и синовиальной жидкости пациентов с деформирующим остеоартрозом коленного сустава в зависимости от величины дефекта внутреннего мыщелка большеберцовой кости

Cytokine imbalance is important for pathogenesis of osteoarthritis. Objective To assess serum and synovium cytokine level in patients with deforming osteoarthritis of the knee joint depending on the size of the medial tibial condyle defect. Material and methods Immunoenzyme technique was used to measure cytokine concentration in peripheral blood and synovium of 74 patients with grade III gonarthritis. Results Serum concentration of IL–1β and IL–4 were significantly higher in presence of small, moderate and extensive condylar defects than that in the control group. Concentration of IL–8, IL–10, TNFα was higher in absence of the defect than that in the controls and there was no statistically significant differences in the groups with small and moderate defects. The highest concentration of the cytokines was observed in the group with defects sized more than 10 mm. Synovium concentration of IL–1β, IL–10 was minimum in absence of condylar defect and there was a tendency of increased concentration with a defect measuring less than 5 mm and it substantially increased with defects measuring more than 6 mm. Synovium concentration of IL–8 was higher than that of the serum but there was no statistically significant differences between IL–6 and synovium TNFα concentration. Conclusions The magnitude of the condylar defect was shown to influence over synovium and serum cytokine concentration. Concentration of both cytokines was the highest with condylar defect sized more than 50 % of the condylar area and 6 mm deep.

Study of products of IL-12 and IL-18 in sperm and blood of men, suffering on oligosymptomatic forms of a chronic urogenital infection

In order to increase the success of treating by family doctor male with infertility, developing the right tactics and optimal treatment regimens, verification of various factors of male infertility is required. From the accuracy of determining the causes of male infertility depends the further study of the pathogenesis of reproduction impairment, which will contribute to the development of effective therapies. More and more facts are being accumulated that point to the important role of immune processes in the pathogenesis of infertility, which provides the basis for studying the levels of cytokines in patients with chronic urogenital inflammatory processes. The objective : study the production of IL-12 and IL-18 cytokines in seminal plasma in males with low asymptomatic forms of chronic urogenital infection depending on fertility. Materials and methods . The patients (n=72) were examined for small asymptomatic forms of chronic inflammation of the urogenital tract, aged from 22 to 40 years. All surveyed are divided into two groups: the first (35 people) – infertile men and the second (37 people) – fertile men. Duration of infertility in patients of the І th group was 3 6 years. Polymerase chain reaction (PCR) method was used to detect Chlamidia trachomatis, M. hominis, U. urealyticum, V. herpes in seminal plasma. At the beginning of the survey, it took more than a year after the completion of the previous treatment. Sperm studies were performed and sperm morphology was determined using staining for Papanicolaou. Levels of IL-12 and IL-18 cytokines were studied in serum and in the semen. Control parameters of cytokine concentrations were obtained during the study of 24 fertile men without clinical signs of a disease of a similar age composition. Results . Investigation of cytokine levels in patients, depending on fertility, found that in the I group (male infertility), the level of IL-12 in the semen tended to decrease, with its concentration in blood in patients in this group did not differ from the norm. As for the group of fertile men (group II), an immunological study indicates diverse shifts in concentrations of IL-12 and IL-18 in both serum and seminal plasma. An increase in the content of the studied cytokines is much more pronounced in the semen than in the serum. The spermometry of both groups of patients showed that hyperfertility and microsomal type of sperma was observed in infertility men, and in fertile men, although there was a normospermia, however, in that part of the patients of the II group, which showed a decrease in the concentrations of IL-12 and IL-18 in the semen we stated an increase in the pathological forms of sperm. The data obtained indicate, in our opinion, the participation of IL-12 and IL-18 in the course of inflammation (mainly increased concentrations) and participation in the process of maturation of sperm. Conclusion . Microenvironment is important during maturation of the germ cells. An important role in this is played by cytokines, in particular IL-12 and IL-18. The study of the concentration of IL-12 and IL-18 in semen is more appropriate than in serum when the inflammatory process is established in the urogenital tract. Reduced concentrations of IL-12 and IL-18 in semen indicate the development of infertility, as evidenced by the presence of pathospermia. Immunocorrection therapy in men with oligosymptomatic forms of chronic inflammation of the urogenital tract complicated by infertility should take into account the shift of the cytokine profile both in serum and in the semen.

The rs2910164 variant is associated with reduced miR-146a expression but not cytokine levels in patients with type 2 diabetes.

Previous reports have demonstrated that genetic variations in microRNAs regulome could affect microRNAs-mediated regulation. Therefore, in the present study we were aimed at (1) comparison of microRNA 146-a (miR-146a) peripheral blood mononuclear cells (PBMCs) and plasma levels between diabetic patients and controls, and (2) investigating the possible association of rs2910164 with miR-146a and its related target genes expression and also serum cytokine levels. The study population consisted of 60 subjects including 30 type 2 diabetes (T2D) patients and 30 controls with determined genotypes for rs2910164. The RNA expression levels were determined by real-time PCR. Moreover, TNF-α, IL-6, IL-10 and IL-1β serum levels were measured using ELISA method. Our results showed that the miR-146a expression levels were significantly decreased in PBMCs (P=0.004) and plasma (P=0.008) samples of patients with T2D compared to healthy participants. In addition, we observed that IRAK1 mRNA expression-but not TLR4, TRAF6 and NFĸB-was significantly increased in patients with T2D compared to controls (P=0.028). The relative expression levels of miR-146a in plasma and PBMCs samples of diabetic patients with the rs2910164 GG genotypes were significantly higher than that in CC (P<0.05). Moreover, no significant differences were found in miR-146a targets and cytokine levels between the rs2910164 different genotypes. Our study demonstrated that miR-146a circulating levels were significantly elevated in controls compared with T2D patients. In addition, we identified that rs2910164-C allele is associated with reduced expression levels of the miR-146a but not its mRNAs targets and cytokine levels in diabetic patients.

Differences in immunomodulatory properties between venlafaxine and paroxetine in patients with major depressive disorder

Inflammatory processes play a crucial role in the pathophysiology of depression, and identifying the specific cytokines targeted by different antidepressants is important for personalized treatment. The aims of this study were to examine whether venlafaxine and paroxetine cause different immunomodulatory effects when used to treat patients with major depression and to clarify the relationships between plasma cytokine levels and the therapeutic effectiveness of these drugs. A total of 91 Han Chinese patients with major depression completed the 8-week paroxetine or venlafaxine treatment and 90 healthy controls were recruited. A multiplex assay was used to measure cytokines levels in patients with major depression before and after an 8-week venlafaxine and paroxetine treatment. Cytokine levels were measured in healthy controls at the baseline. The 21-item Hamilton Depression Rating Scale was used to assess the changes in psychopathological symptoms from the baseline to the end point in each patient. Venlafaxine treatment caused greater decreases in the levels of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), interleukin 4 (IL-4), IL-5, IL-1β, and IL-8 than did paroxetine. Paroxetine treatment increased the levels of proinflammatory cytokines IFN-γ, TNF-α, and IL-6 and decreased Th2 cytokine levels. After paroxetine treatment, IL-6 levels increased more in the non-remitter group than in the remitter group. In the remitter group, IL-4 and IL-5 levels decreased to values seen in the healthy controls. After venlafaxine treatment in both the remitter and non-remitter groups, IL-1β levels decreased to values seen in the healthy controls. Our results suggest that venlafaxine and paroxetine have different immunomodulatory properties and that venlafaxine has greater anti-inflammatory effects than paroxetine.

Evaluation of Serum TNF-alpha, IL-6, IL-10, and IFN-gamma Levels in Patients with Crimean–Congo Hemorrhagic Fever

BackgroundCrimean–Congo hemorrhagic fever (CCHF) is a potentially fatal disease caused by a tick-borne virus from the Bunyaviridae family. Cytokines plays an important role in the pathogenesis of viral, bacterial, and immunologic diseases. This study aimed to investigate the role of TNF-alpha, IL-6, IL-10, and IFN-gamma levels in the severity of infection and clinical outcome of patients with CCHF.MethodsPatients with confirmed CCHF were divided into two groups (severe cases: Patients who exhibited hemorrhage during their hospital stay, and mild/moderate cases: Patients who displayed no hemorrhage during their hospital stay). Demographic characteristics, laboratory tests on admission of all patients with CCHF were investigated, and serum TNF-alpha, IL-6, IL-10, and IFN-gamma levels were measured.ResultsA total of 154 patients with confirmed CCHF were investigated. Forty-six (29.9%) of these patients were in the severe group. In patients with severe CCHF, significantly higher serum levels of TNF-alpha (68.2 ± 23.5; P = 0.008) and IL-6 (73.1 ± 41.6; P = 0.003) were detected, compared with cytokine levels in patients who mild/moderate CCHF (Table 1). No differences in serum IL-10 and IFN-gamma levels between patients who severe CCHF and those who mild/moderate CCHF were detected (P > 0.05).Table 1: Cytokine levels, demographic and laboratory characteristics in patients with severe and mild/moderate cases with CCHF.FeaturesSevere cases n = 46Mild/moderate cases n = 108 P-valueAge50.6 ± 20.349.8 ± 21.00.682Female gender, n (%)31 (67.4)63 (58,3)0.291 TNF- 68.2 ± 23.5 41.3 ± 17.4 0.008 IL-6 73.1 ± 41.6 38.0 ± 19.5 0.003 IL-106.32 ± 1.36.21 ± 1.40.753IFN-gamma145 ± 96126 ± 920.664WBC3286 ± 5,6022,275 ± 1,2860.280 PLT 53,564 ± 36,520 98,065 ± 42,768 0.001 CRP 3.2 ± 2.6 1.1 ± 1.4 0.005 ALT 521 ± 482 208 ± 320 0.044 AST 869 ± 1.182 256 ± 215 0.016 CPK 1,138 ± 970 676 ± 835 0.007 LDH 1,800 ± 1,254 589 ± 271 0.002 ConclusionCytokines, chemokines, and other inflammatory mediators function in a manner, acting on many different cell types to regulate the host’s immune response. When cytokines present in high concentrations, they might toxic or even lethal effects. In accordance with this view, we have detected increased serum TNF-alpha, IL-6 levels in the patients with severe CCHF.Disclosures All authors: No reported disclosures.