Anti-inflammatory Cytokine Concentrations Research Articles

Evaluation of the relationship between anti-inflammatory cytokines and adverse cardiac remodeling after myocardial infarction.

Aim To clarify the role of interleukin (IL) - 10 and members of its subfamily (IL-19 and IL-26) in cardiac remodeling during the post-myocardial infarction (MI) period.Material and methods A total of 45 patients with ST-segment elevation MI were enrolled. Serum cytokine concentrations were measured at the first day and 14 days post-MI. Left ventricular (LV) reverse remodeling (RR) was defined as the reduction of LV end-diastolic volume or LV end-systolic volume by ≥ 12 % in cardiac magnetic resonance images at 6‑mo follow-up. A 12 % increase was defined as adverse remodeling (AR).Results The post-MI first-day median IL-10 (9.7 pg / ml vs. 17.6 pg / ml, p<0.001), median IL-19 (28.7 pg / ml vs. 36.9 pg / ml, p<0.001), and median IL-26 (47.8 pg / ml vs. 90.7 pg / ml, p<0.001) were lower in the RR group compared to the AR group. There was a significant decrease in the concentration of anti-inflammatory cytokines in the AR group from the first to the 14 days post-MI. However, no significant change was observed in the RR group. Regression analysis revealed that a low IL-10 concentration on the post-MI first day was related to RR (OR=0.76, p=0.035). A 1 % increase in change of IL-10 concentration increased the probability of RR by 1.07 times.Conclusion The concentrations of cytokines were higher in the AR group, but this elevation was not sustained and significantly decreased for the 14 days post-MI. In the RR group, the concentrations of cytokines did not change and stable for the 14 days post-MI. As a reflection of this findings, stable IL-10 concentration may play a role the improvement of cardiac functions.

Markers of progression of liver fibrotic changes in patients with chronic toxic drug-induced hepatitis

Background. In recent years, as a result of the growing expansion of the pharmaceutical market, there has been a clear trend towards an increase in the incidence of chronic toxic drug-induced hepatitis of drug genesis (TDIH). The appearance of fibrosis is considered the most important histological change that determines the further course of the disease. Therefore, the search for non-invasive or minimally invasive markers for assessing fibrotic changes in the liver remains an urgent issue in clinical practice. The purpose was to determine the diagnostic value of immunological parameters for stratification of the severity of liver fibrosis in patients with TDIH. Materials and methods. The study included 41 patients with TDIH, who were divided into three groups: group I consisted of 12 people without liver fibrosis (F0), group II— 22 patients with moderate fibrosis (F1-F2), group III— 7 individuals with severe liver fibrosis (F3-F4). Shear wave elastography was performed using a Soneus P7 system (Ukraine-Switzerland). All patients underwent a biochemical blood test with the determination of alanine aminotransferase (ALT), aspartate aminotransferase (AST). The subpopulation composition of lymphocytes, circulating immune complexes (CIC), the level of interleukins (IL-6, IL-10) and tumor necrosis factor α were assessed. Results.The progression of liver fibrosis is accompanied by an increase in cytolytic syndrome: patients with severe fibrosis have a 3.3-fold increase in the ALT (p<0.05) compared to the controls and a 2.1-fold (p<0.05) compared to that in patients with moderate fibrosis. The AST level is significantly higher— by 4.6 times (p=0.023) in patients with severe fibrosis than in those with moderate fibrosis. With the progression of liver fibrosis, there is a significant decrease in cellular immunity, an increase in the level of CIC and pro-inflammatory cytokines with a simultaneous decrease in the content of anti-inflammatory cytokines, which is confirmed by correlations between the liver stiffness index according to shear wave elastography data and the level of T-helpers (r=–0.466; p=0.03), IL-6 (r=0.364; p=0.01), IL-10 (r=–0.331; p=0.039) and CIC (r=0.381; p=0.017). Conclusions. Markers of the diagnosis of severe liver fibrosis in patients with TDIH are indicators such as the ratio of IL-6/IL-10 higher than 0.83 (sensitivity 81.8%, specificity 78.9%), CIC level more than 4.3 optical density units (sensitivity 77.3%, specificity 72.2%), the ratio of T-helpers/T-suppressors is less than or equal to 1.6 (sensitivity 72.7%, specificity 57.9%).

Capecitabine Can Induce T Cell Apoptosis: A Potential Immunosuppressive Agent With Anti-Cancer Effect.

Capecitabine (CAP) is now widely used in the comprehensive treatment of digestive system tumors. Some clinical observations have shown that CAP may have immunosuppressive effects, but there is still a lack of clear experimental verification. In this study, different doses of CAP were administered to normal mice by gavage. Our results confirmed that CAP did not cause myelosuppression in bone marrow tissue; CAP selectively reduced the proportion of T cells and the concentration of related pro-inflammatory cytokines, while it increased the concentration of anti-inflammatory cytokines. Thymidylate phosphorylase (TP) is the key enzyme for the transformation of CAP in vivo; this study confirmed that T cells express TP, but the bone marrow tissue lacks TP expression, which explains the selectivity in pharmacodynamic effects of CAP. In addition, it was confirmed that CAP can induce T cell apoptosis in vivo and in vitro. In vitro experiments showed that CAP-induced T cell apoptosis was related to TP expression, endoplasmic reticulum stress (ERS) induction, reactive oxygen species (ROS) production, and mitochondria-mediated apoptosis activation. Therefore, this study confirmed that the differential expression of TP in cells and tissues explains why CAP avoids the toxic effects of myelosuppression while inducing T cell apoptosis to exert the immunosuppressive effect. Therefore, CAP may become an immunosuppressive agent with a simultaneous anti-cancer effect, which is worthy of further studies.

Stress-induced pro- and anti-inflammatory cytokine concentrations in PTSD and MD patients

Stress-induced pro- and anti-inflammatory cytokine concentrations in PTSD and MD patients

Cytokines and Chemokines Involved in Osteoarthritis Pathogenesis.

Osteoarthritis is a common cause of disability worldwide. Although commonly referred to as a disease of the joint cartilage, osteoarthritis affects all joint tissues equally. The pathogenesis of this degenerative process is not completely understood; however, a low-grade inflammation leading to an imbalance between anabolic and katabolic processes is a well-established factor. The complex network of cytokines regulating these processes and cell communication has a central role in the development and progression of osteoarthritis. Concentrations of both proinflammatory and anti-inflammatory cytokines were found to be altered depending on the osteoarthritis stage and activity. In this review, we analyzed individual cytokines involved in the immune processes with an emphasis on their function in osteoarthritis.

Clinical and economic constituents of the application of dexamethasone and tocilizumab in the therapy for severe conditions in patients with COVID-19

Background. Severe forms of COVID-19 are associated with the development of a cytokine storm that is characterized by an increased secretion of anti-inflammatory cytokines. Thus, one of the leading strategies of treatment for patients with severe forms of COVID-19 is a decrease in the concentration of anti-inflammatory cytokines and inhibition of their effect on the organism.Objective: to perform a comparative analysis of clinical and economic constituents of the application of an IL-6 inhibitor tocilizumab and systemic glucocorticosteroid dexamethasone for the therapy of severe conditions in patients with COVID-19 based on the published data review.Material and methods. The authors analyzed the data obtained from PubMed/MEDLINE databases on the study dedicated to the application of tocilizumab and dexamethasone for the therapy of severe conditions in patients with COVID-19. A statistical evaluation of the influence of these drugs on the 28-day survival rate of patients with a severe form of COVID-19 was performed. The statistical tools included methods of the attribute-based statistic (attribute-based efficiency, relative efficiency (RE), populational attributive efficiency (PAE)). For the visualization of the clinical efficiency of the compared drugs, the authors applied beta-distribution. Markov’s model was used for modeling of the mortality rate. The modeling included the study of a hypothetical cohort of patients (1,000 patients with COVID-19). Besides, the authors evaluated the economic constitutive of the therapy with tocilizumab and dexamethasone. The cost-effectiveness analysis was performed.Results. The indication of dexamethasone statistically significantly increases the survival rate by 3.1% and tocilizumab – by 22.5%. RE was 1.04 (95% CI 0.040–2.042) for dexamethasone and 1.66 (95% CI 0.400–2.917) for tocilizumab. The lower border of 95% CI for both drugs was within the range of values <1, which was statistically significant. PAE for dexamethasone was 1.0% (95% CI –0.6–2.6), for tocilizumab – 16.5% (95% CI –0.7–33.7). Lower borders of 95% CI for both drugs ranged within negative values, which was not statistically significant. NNT (dexamethasone) was 32; NNT (tocilizumab) was 4. Markov’s modeling showed that the mortality rate among patients who received these drugs was 36 out of 1000 patients with COVID-19 for dexamethasone (initially distributed by the degree of severity according to the official statistical data) and 30 out of 1000 patients for tocilizumab, respectively. The cost of the treatment course with dexamethasone was 107.45 rub., tocilizumab – 78,827.20 rub. Clinical efficiency by the rate of cured patients obtained as a result of Markov’s modeling among patients with severe forms of COVID-19 for both drugs was comparable (0.964 for dexamethasone and 0.970 for tocilizumab) with slightly higher values for tocilizumab.Conclusion. Despite relatively comparable clinical efficiency of dexamethasone and tocilizumab and a significantly higher cost the later, it is not impossible to replace tocilizumab with dexamethasone because of a great number of side effects and potential inter-drug interactions during the treatment of severe forms of COVID-19. In particular, dexamethasone therapy should be performed with caution in patients with diabetes mellitus. Procurement planning should be made taking account the reserves of tocilizumab for the stabilization of patients with cytokine storm when dexamethasone application is not safe.

Significant immunomodulatory and hepatoprotective impacts of Silymarin in MS patients: A double-blind placebo-controlled clinical trial

Interferon beta (IFN-β) has successfully been experimented with to treat multiple sclerosis (MS). However, patients sometimes do not respond effectively to treatment, and ‌adverse effects, including liver toxicity, accompany this therapy. ‌Accordingly, we decided to treat MS patients simultaneously with Silymarin (SM) as an immunomodulatory and hepatoprotective agent and IFN-β in a clinical trial study.Complete blood count (CBC), liver enzyme levels, and the serum concentration of inflammatory and anti-inflammatory cytokines were measured. Also, the frequency of immune cells was determined by flow cytometry.Liver enzyme levels were significantly lower in the intervention group (p < 0.05). The percentage of Th17 cells in the intervention group was significantly reduced compared to the placebo group (P < 0.001). Also, the frequency of Treg cells after treatment with SM plus IFN-β was significantly increased compared to the placebo group (p < 0.05). Furthermore, the IL-17 and IFNγ cytokine levels were significantly reduced in the intervention group (p < 0.05). Moreover, the levels of anti-inflammatory cytokines IL-10 and TGFβ were significantly increased in the intervention group (P < 0.05).Overall, the results provide novel and supplementary information on SM’s notable immunoregulatory effects on inflammatory response and liver function in MS patients.Clinical Trial Identifier Number: IRCTID: IRCT20171220037977N1.

Trier Social Stress Test Does Not Produce a Cytokine Reaction in Adolescence

Immune system activation has been postulated as one of the mechanisms linking stress to the manifestation of psychiatric conditions. In adults, both the Trier Social Stress Test (TSST) and the bacterial endotoxin Lipopolysaccharide (LPS) are known to stimulate the immune system, resulting in elevated inflammatory and decreased anti-inflammatory cytokine concentrations in the blood. Our study aimed to reproduce these effects in adolescences.

The Use of Autologous Protein Solution (Pro-Stride®) and Leukocyte-Rich Platelet-Rich Plasma (Restigen®) in Canine Medicine.

The use of autologous orthobiologics is an emerging area of interest in veterinary medicine. In this retrospective study, we reviewed the clinical results achieved using two orthobiologics devices to address orthopedic injuries and tissue repair. Leukocyte (White blood cell)-rich platelet-rich plasma (L-PRP) devices produce outputs containing high concentrations of growth factors from venous blood. The Autologous Protein Solution (APS) device produces an orthobiologic containing high concentrations of growth factors and anti-inflammatory cytokines. L-PRP has commonly been used to address soft tissue injuries. APS has been injected into the joint to address osteoarthritis. In the last five years, our practice has treated 35 dogs (38 treatments) with L-PRP and 98 dogs (108 treatments) with APS. Our group has used L-PRP and APS to address orthopedic conditions including osteoarthritis, bursitis, tendinitis, tendon/ligament rupture/repair procedures, post-surgical femoral head osteotomy/tibial-plateau-leveling osteotomy tissue repair, lumbosacral stenosis, patellar luxation, joint laxity, and osteochondral dissecans. The results achieved with L-PRP and APS have been favorable (observed pain improvement and minimal adverse reactions), but sometimes have not achieved complete pain relief or tissue repair. The most common application for L-PRP was patellar luxation and the most common application for APS was injection post-ACL surgery. Canine OA has been successfully managed in several patients with repeat injections of APS over the course of several years. Future studies on specific conditions are ongoing and including efforts to further characterize these products in canine medicine.

Дифференцировка моноцитов крови и особенности цитокинового статуса у больных туберкулезом легких

In clinical manifestation of pulmonary tuberculosis, alveolar macrophages perform as a reservoir where they accumulate mycobacteria and lose their effector functions due to the pathological conversion of macrophage pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype, which provides transition to chronic infection. The study hypothesis suggested that the cytokine status, as evaluated by leukocyte secretion of cytokines in vitro, influences the monocyte polarization in the blood during their migration to the inflammatory focus, thereby determining differentiation and pathways of macrophage activation in tissues.The aim of this work was to assess the immunophenotype of blood monocytes and the in vitro secretion of immunoregulatory cytokines by mononuclear peripheral blood leukocytes from patients with different clinical forms of pulmonary tuberculosis taking into account the pathogen sensitivity to major anti-tuberculosis drugs.Methods. 65 patients with newly diagnosed pulmonary tuberculosis were evaluated. The study material was venous blood and peripheral blood mononuclear leukocytes. Monocyte immunophenotype was determined in whole blood by flow cytometry on a Cytoflex flow cytometer (Becman Coulter, USA) with monoclonal antibodies (eBioscience, USA). Results were processed with a CytExpert 2.0 software. The number of cells expressing surface markers, CD14, CD163, CD204 and HLA-DR, was determined. Content of cytokines (IL-2, IL-10, TGFβ) in supernatants of cell cultures was measured by enzyme-linked immunosorbent assay (ELISA). Results of the study were processed with a SPSS v.11.0 standard software package.Results. The study results suggested that with an overall decrease in the number of circulating CD14-positive blood monocytes in patients with pulmonary tuberculosis regardless of its clinical form, high expression of cell activation markers remained both for the pro-inflammatory M1 phenotype (HLA-DR-positive monocytes) and the anti-inflammatory M2 phenotype (CD163-positive monocytes). In disseminated tuberculosis, the number of anti-inflammatory CD204-positive monocytes, M2 macrophage precursors, increases indicating predomination of the immunosuppressive response. In vitro analysis of the cytokine status showed that tuberculosis progression is accompanied by inhibition of effector immune responses and increases in anti-inflammatory cytokine concentrations in vitro. These changes may be equally either a cause or a consequence of deficient IL-2 secretion. We also found that the secretion of mediators with suppressor effects (IL-10, TGFβ) varied depending on both the clinical form of tuberculosis and the pathogen sensitivity to anti-TB drugs; IL-10 hypersecretion was observed in patients with drug-sensitive, infiltrative tuberculosis whereas TGFβ hypersecretion was observed in disseminated, drug-resistant tuberculosis.Conclusion. Features of blood monocyte differentiation in patients with pulmonary tuberculosis allowed us to conclude that monocytes, the macrophage precursors, start expressing markers for different functions of M1 and M2 macrophages with polarization toward the M2 immunophenotype already in the bloodstream. Therefore, in the development of pulmonary tuberculosis, cytokine regulation mechanisms become involved in suppressing the activation of innate immunity, which possibly causes chronic inflammation in the lungs and formation of Mtb-induced immunodeficiency.

Studies on Immunomodulatory Effect of Casein Phospho Peptide Isolated from Cultured Dairy Product

Bioactive peptides have been defined as specific protein fragments that have an impact on body functions or conditions and may ultimately influence health. Fermented milk is a dairy product which has abundance of bioactive peptides. In this study, Casein Phospho peptide (CPP) was isolated by enzymatic hydrolysis of fermented milk using trypsin. The molecular weight of the Casein Phospho peptide was 3.5 KDa. The anti-bacterial activity of Casein Phospho peptide was determined using four pathogens such as, Escherichia coli, Bacillus cereus, Staphylococcus aureus and Salmonella enterica. Casein phospho peptide formed a zone of inhibition against the pathogens. The bioactive peptides were characterized using Fourier Transform Infra-Red Spectroscopy (FT-IR), Casein Phospho peptide had aliphatic amine, acetyl amino I and acetyl amino II functional groups. The HPLC analysis of Casein Phospho peptide revealed that the major amino acid present was L- Glutamic acid and the amino acid present in lesser concentration was Leucine. Peripheral Blood Mononuclear Cells (PBMCs) were isolated from human blood and the cells were treated with Casein Phospho peptide to assess the immunomodulatory effect.&#x0D; Casein Phospho peptide was able to produce a higher concentration of IL-10 anti-inflammatory cytokines when treated with PBMCs.

Justification of the need to normalize vitamin D status for immunoprophylaxis

Currently, there is an increase in the resistance of microorganisms to the available arsenal of antimicrobial drugs, which makes it necessary to maintain and stimulate the body's own immune-protective properties. The main extraskeletal effect of vitamin D activity is associated with the homeostasis of the immune system. The role of vitamin D in reducing the risk of infection with infectious agents has been studied for a long time. Literature search on the effective use of vitamin D for immunoprophylaxis was carried out in Scopus, Web of Science, PubMed, clinicaltrials.gov databases over the past 10 years for related keywords: vitamin D, immunoprophylaxis. Vitamin D stimulates the synthesis of antimicrobial peptides, cathelicidins and defensins, which exhibit broad-spectrum activity against viruses, bacteria and fungal infections; reduces the concentration of pro-inflammatory cytokines; increases the concentration of anti-inflammatory cytokines. Vitamin D is also involved in cell differentiation, maturation and proliferation of immune cells. The article presents the literature review in order to justify additional intake of vitamin D in case of diagnosis of its deficiency and insufficiency for the purpose of immunoprophylaxis in children and adults, especially in risk groups (elderly age, pregnant women, patients with chronic diseases of respiratory, endocrine and urinary systems, gastrointestinal tract, and infectious diseases). Inclusion of vitamin D in the diet as a dietary supplement, as well as fortification of products with it, can be an effective measure to reduce the risk of both morbidity and mortality, especially during the period of quarantine measures.

Cerebrospinal Fluid Cytokines in Patients with Neurosyphilis: The Significance of Interleukin-10 for the Disease.

The aim of this study was to examine the cerebrospinal fluid (CSF) concentrations of proinflammatory and anti-inflammatory cytokines in neurosyphilis (NS), analyze the differences between asymptomatic NS (ANS) and symptomatic NS (SNS), and explore the diagnostic value of these cytokines. We enrolled 45 patients with a diagnosis of NS, including 18 patients with ANS and 27 patients with SNS, whose cerebrospinal fluid (CSF) samples were collected before penicillin therapy. Twelve patients with syphilis but non-NS (NNS) were also included. We measured the CSF levels of interleukin- (IL-) 1β, IL-4, IL-6, IL-10, IL-17A, IL-21, and tumor necrosis factor- (TNF-) α; the CSF levels of the microglial activation marker soluble triggering receptor expressed on myeloid cells 2 (sTREM2); and the CSF levels of the neuronal injury marker neurofilament light proteins (NFL) using the human cytokine multiplex assay or ELISA. Of the measured cytokines in the CSF, only IL-10 levels were significantly increased in NS patients compared to NNS patients (p < 0.001). In a subgroup analysis, the CSF levels of IL-10 were significantly elevated in SNS patients compared to ANS and NNS patients (p = 0.024 and p < 0.001, respectively). The CSF IL-10 levels had a significant correlation with the markers of microglial activation and neuronal injury, and they also correlated with CSF rapid plasma reagin (RPR) titer, CSF white blood cell (WBC) count, and CSF protein concentration. The areas under the ROC curve (AUC) of CSF IL-10 in the diagnosis of NS and ANS were 0.920 and 0.891, respectively. The corresponding sensitivities/specificities were 86.7%/91.7% and 83.3%/91.7%, respectively. Therefore, the excessive production of IL-10 might facilitate bacterial persistent infection, play an important role in the pathogenesis of NS, and associate with the progression of the disease. CSF IL-10 concentration had a useful value in the diagnosis of NS, especially in ANS.

Combination of candida vulvovaginitis and bacterial vaginosis: optimization of diagnostics and treatment for the women of genesial age

The objective: increase of efficiency of diagnostics and treatment of combination of candida vulvovaginitis and bacterial vaginosis for the women of genesial age on the basis of study of new aspects of pathogeny and improvement of algorithm of prognostic and treatment-and-prophylactic measures.Materials and methods. Researches carried stage-by-stage character. The I stage is development of the special questionnaire for a selection, account and bringing of master data. In it taken into account: age, social information, anthropometric descriptions, anamnesis of gynaecological diseases, somatic pathology. II stage is the conducted selection 150 women with the identical clinical displays of candida vulvovaginitis and bacterial vaginosis, which before did not treat oneself and produced characteristic complaints about appearance of pathological excretions from sexual ways, itch of vulva, burning at urination. At gynaecological examination: hyperemia, edema of vulva, mucous membranes of vagina and cervix of uterus, «curd» or watery excretions. III stage is an estimation of the got material and setting of treatment. On every woman «Map of clinical-laboratory researches», in which brought in information of anamnesis, results of inspection from history of illness and ambulatory card, was led, to the fame about a presence and completion of inflammatory diseases of organs of small pelvis, results of bacteriological, microbiological, taking about tactic of conduct and result of treatment.For comparison of efficiency of treatment 150 patients with identical clinical displays and presence of Candida albicans, non-albicans and «key» cages part on 3 groups. Estimation of efficiency of the algorithm improved by us was conducted on three criteria: general state and feel of patients, clinical information (information of anamnesis and gynaecological review), laboratory and backterioscopy information. All methods of research answered ethics standards, developed in accordance with Helsinki declaration of the World medical association «Ethics principles of leadthrough of scientific medical researches with participation of man».Results. For early diagnostics of combination of vulvovaginal candidiasis and bacterial vaginosis the use of a twostage method of individual prognostication is needed on the basis of model of mathematical structural boolean algebra with the obligatory estimation of the most informing indexes: expression of molecules of adhesion of vascular walls (VCAM-1) and intercellular molecules of adhesion (ICAM-1); concentration of anti-inflammatory cytokines (4, 6 and 8).Conclusion. With the purpose of increase of efficiency of treatment of combination of vulvovaginal candidiasis and bacterial vaginosis the additional use is needed 1–2 hours prior to the combined therapy of local correction 0,01% solution of preparation of miramictine. Efficiency of the use for women at combination of vulvovaginal candidiasis and bacterial vaginosis of the combined anti-inflammatory therapy (miconazole and metronidazole) is 92,0%; in combination with probiotic – 98,0% and with immunocorrector of local action – 100,0%.

Mechanism of stress heart damage in the animals of different sensitivity to hypoxia

Hypoxia and resistance to it is the main in today data sitiuayion in the world.The aim of the study was to determine level of myocardium damage and corresponding of it with cytokines level in high- and low-resistance to hypoxic hypoxia rats (HR, LR) in different models of immobilization stress.Material and methods of investigation. The experiments were performed on 144 outbred HR and LR aged 5.5-6 months, dividing into 3 groups – control and 2 with different model of immobilizing stress. It was determined morphological changes of myocardium and concentration of interleukins 1beta, 2, 4, 6, 10 (IL-1beta, IL-2, IL-4, IL-6, IL-10), tumor necrosis factor alpha (TNF-alpha) in the blood serum.Results. The morphological investigation showed the bigger damage effect in LR animal, than in HR rats. Damage effects were higher in males, than in females. The stress repeating every 72 hours (stress 2) had higher damage in myocardium, than stress repeating every 24 hours (stress 1). We corresponds the results with cytokines level. High congenital resistance to hypoxia is associated with an increased content of anti-inflammatory cytokines (in males IL-4, in females IL-10). Intact males, compared with females, have a higher production of pro-inflammatory cytokines (IL-6, TNF-alpha).At stress1 inHR males, compared with HR females, were lower contents of IL-10, higher level of IL-1beta, IL-4, IL-6, TNF-alpha. At stress1 inLR males, compared with LR females, were lower contends of IL-10, IL-2. The morphological changes were more in males, that’s why higher level of anti-inflammatory cytokines IL-10 really has protection in HR and LR females’ animals. At stress2 inHR male, compared with HR female, were lower contents of IL-1beta and IL-10, higher IL-2 and IL-6. At stress2 inLR males, compared with LR females, were higher level of IL-10, IL-6, lower contents of IL-2, IL-4. The morphological changes were more in males, that’s why pro-inflammatory cytokines IL-6 really take place in damage of myocardium in males with different resistance animals.Conclusion. High congenital resistance to hypoxia is associated with smaller destroying of the myocardium layer in immobilizing stress, which correspond with increased content of anti-inflammatory cytokines IL-4 and, IL-10. Higher damage of myocardium in immobilizing stress correspond with higher production of pro-inflammatory cytokines (IL-6, TNF-alpha).

Comparative clinical and epidemiological characteristics and cytokine profile of viral diarrhea in adults

The aim of the work is to determine the clinical and pidemiological features and indicators of the cytokine profile in patients with viral diarrhea in the adult population, to establish the influence of inflammatory mediators on the course of the disease. Materials and methods -we analyzed the patient’s hospital records, as well as the blood serum of patients diagnosed with viral diarrhea. The experimental group consisted of 29 patients aged 23,2 ±8,4, with an equal distribution among men and women. The 1 experimental group included 22 patients with norovirus infection, the 2 comparison group consisted of 7 people with rotavirus gastroenteritis. The control group consisted of 20 somatically healthy people of the appropriate age (23,3±1,4). The concentration of proinflammatory and anti-inflammatory cytokines in blood serum was determined by ELISA using reagents from Vector-best LLC (Novosibirsk). Statistical processing of the obtained data was carried out using electronic programs Microsoft Excel 2010, Statistica 6.0, with the determination of the statistical significance of differences at the achieved significance level p ≤ 0.05 using the Mann – Whitney test (U-test). When calculating correlations, we used Spearman’s coefficient, r = -1+1 (r=0-0, 3 – weak connection, r= 0,3–0,7 – medium strength connection, r= 0,7–1 – strong connection; «+» – direct connection, «–» – feedback). The distribution of features was evaluated using the Shapiro – Wilkes W test. Results : in the course of work, the prevalence of norovirus infection among adult patients with viral diarrhea was established. Among the ways of infection, the food and water routes predominated, contact and household was noted, mainly, when caring for children with intestinal infection. In the clinical picture, all patients had a moderate intoxication syndrome. With rotavirus infection, catarrhal and pronounced gastroenteritis syndromes were determined, while for norovirus gastroenteritis, catarrhal syndrome was not characteristic, and patients also had a tendency to constipation. When assessing the cytokine status, an increase in the concentration of IL-2, IL-6, TNF- α , IL-10 was found, regardless of the etiological factor, at normal levels of IL-1 β and low IL-4, as well as a strong direct dependence of the severity of feverish intoxication syndrome on the level of IL-2, IL-1 β and IL-4. The effect of Pro-inflammatory and anti-inflammatory cytokine production on the duration of individual syndromes and on the duration of the disease as a whole has not been established. Conclusion – norovirus infection, in contrast to rotavirus infection, occurs without an obvious respiratory catarrhal syndrome, with the predominance of intoxication over gastroenteritis, while in rotavirus infection, the syndrome of intoxication and gastroenteritis are expressed equally. In viral diarrhea, there is an increase in IL-2, IL-6, TNF-a, and IL-10, which play an important role in the development of feverintoxication syndrome and the formation of antiviral protection.

Berberine Administration in Treatment of Colitis: A Review.

Berberine (Brb) is one of the well-known naturally occurring compounds exclusively found in Berberis vulgaris and other members of this family, such as Berberis aristata, Berberis aroatica, and Berberis aquifolium. This plant-derived natural compound has a variety of therapeutic impacts, including anti-oxidant, anti-inflammatory, anti-diabetic, and anti-tumor. Multiple studies have demonstrated that Brb has great anti-inflammatory activity and is capable of reducing the levels of proinflammatory cytokines, while it enhances the concentrations of anti-inflammatory cytokines, making it suitable for the treatment of inflammatory disorders. Colitis is an inflammatory bowel disease with chronic nature. Several factors are involved in the development of colitis and it appears that inflammation and oxidative stress are the most important ones. With respect to the anti-inflammatory and antioxidant effects of Brb, its administration seems to be beneficial in the treatment of colitis. In the present review, the protective effects of Brb in colitis treatment and its impact on molecular pathways are discussed.

IL-33 and its decoy sST2 in patients with Alzheimer\u2019s disease and mild cognitive impairment

BackgroundInterleukin-33 is a cytokine endowed with pro- and anti-inflammatory properties that plays a still poorly defined role in the pathogenesis of a number of central nervous system (CNS) conditions including Alzheimer’s disease (AD). We analyzed this cytokine and its decoy receptor sST2 in Alzheimer’s disease (AD) and mild cognitive impairment (MCI).MethodIL-33 and sST2 were analyzed in serum and CSF of AD and MCI patients, comparing the results to those obtained in age-matched healthy controls (HC). Because of the ambiguous role of IL-33 in inflammation, the concentration of both inflammatory (IL-1β and IL-6) and anti-inflammatory (IL-10) cytokines was analyzed as well in serum and cerebrospinal fluid (CSF) of the same individuals. Finally, the effect of IL-33 on in vitro Aβ42-stimulated monocytes of AD, MCI, and HC individuals was examined.ResultsAs compared to HC, (1) IL-33 was significantly decreased in serum and CSF of AD and MCI, (2) sST2 was increased in serum of AD and MCI but was undetectable in CSF, (3) serum and CSF IL-1β concentration was significantly increased and that of IL-10 was reduced in AD and MCI, whereas no differences were observed in IL-6. In vitro addition of IL-33 to LPS+Aβ 42-stimulated monocytes downregulated IL-1β generation in MCI and HC, but not in AD, and stimulated IL-10 production in HC alone. IL-33 addition also resulted in a significant reduction of NF-kB nuclear translocation in LPS+Aβ42-stimulated monocytes of HC alone.ConclusionsThese data support the hypothesis that IL-33 plays a complex anti-inflammatory role that is lost in AD- and MCI-associated neuroinflammation; results herein also suggest a possible use of IL-33 as a novel therapeutic approach in AD and MCI.

The cytokine system’s status in bacterial dysbiosis and bacterial vaginosis

Interrelations of conditionally-pathogenic microflora and vaginal mucosa’s APC are realized by forming of proinflammatory and regulatory cytokines which can provoke bacterial dysbiosis progression and bacterial vaginosis development.The aim of the study: to determine cytokine system’s status in the blood and vaginal fluid in bacterial dysbiosis and bacterial vaginosis.Material and methods. There were used data from 298 women, divided into groups according to the index of conditionally pathogenic microflora and normobiota index: normocenosis (n=53); grade I bacterial dysbiosis (n=128); and grade II bacterial dysbiosis (n=117). In the last group 83 patients with normobiota index &gt;1 lg GE/sample, with bacterial vaginosis isolated. The posterolateral vaginal paries epithelium scrapings examined with PCR: facultative and obligate anaerobes, myco- and ureplasms and yeast fungi were quantified. Contents of IL in VF and in the serum were studied with enzyme-linked immunosorbent assay. For statistical analysis Statistica 10 soft (StatSoft, Inc., USA) was applied.Results. Blood interleukins’ contents increased with progressing of bacterial dysbiosis, and was maximal in bacterial vaginosis: 3,0-6,0 times (p&lt;0,001) more than in normocenosis. Levels of these interleukins were: interleukin-1β &gt; interleukin-6&gt;interleukin-8&gt;tumour necrosis factor-α &gt; interleukin-2; in vaginal fluid: interleukin-6&gt; tumour necrosis factor-α &gt; interleukin-1β&gt;interleukin-8&gt; interleukin2. Content of γ-interferon in blood and vaginal fluid was higher in bacterial dysbiosis, and was less in manifested bacterial dysbiosis and bacterial vaginosis (comparing to normocenosis). Interleukin-4 and interleukin-10 levels were less in the blood and vaginal fluid along to the progressing of bacterial dysbiosis. Transforming growth factor-1β level in the blood was more in bacterial vaginosis only, whereas in vaginal fluid –in bacterial dysbiosis and bacterial vaginosis. Among blood cytokines interleukin-1β levels correlated with index of conditionally-pathogenic microflora: its content more 24,6 pg/ml indicated bacterial dysbiosis-II, from 9,6 to 24,5 pg/ml –bacterial dysbiosis-I, and contents less than 9,6 pg/ml – normocenosis. Transforming growth factor-1β and interleukin-10 contents in vaginal fluid were suppressive.Conclusion. Obtained data confirmed determining role of cytokine system in bacterial dysbiosis progression and bacterial vaginosis development. Content of proinflammatory cytokines in the bloodstream increased with progressing of dysbiosis and reached maximum I bacterial vaginosis. Content of anti-inflammatory cytokines with progressing of dysbiosis decreased both in the bloodstream and vaginal fluid

Changes in the content of interleukins in the serum of male and female rates with different resistance to acute hypoxic hypoxia under immobilization stress

Attention of scientists of the world are study the features of increased resistance to hypoxia and stress, different development inflammation in them.The aim of the study was to trace the features of interleukins level in high- and low-resistance to hypoxic hypoxia rats (HR, LR) in different models of immobilization stress.Material and methods of investigation. The experiments were performed on 144 outbred HR and LR aged 5.5-6 months, dividing into 3 groups – control and 2 with different model of immobilizing stress. Determine concentration of interleukins 1beta, 2, 4, 6, 10 (IL-1beta, IL-2, IL-4, IL-6, IL-10), tumor necrosis factor alpha (TNF-alpha) in the blood serum.Results. High congenital resistance to hypoxia is associated with an increased content of anti-inflammatory cytokines (in males - IL-4 on 24.73% (p&lt;0.001), in females - IL-10 on 37.36%; p&lt;0.001). Intact males, compared with females, have a higher production of pro-inflammatory cytokines (IL-6, TNF-alpha). Intact males, compared with females, are dominated by the content of pro-inflammatory cytokines in the blood. In HR males, compared with females, a higher content of IL-6 (49.93%; p&lt;0.01), TNF-alpha (10.85%; p&lt;0.01), IL-4 (33.92%; p&lt;0.001), lower - IL-1beta (37.91%; p&lt;0.02) and IL-10 (93.06%; p&lt;0.001). In LR males, compared with females, higher blood levels of IL-1beta (42.98%; p&lt;0.001), IL-6 (54.32%; p&lt;0.001), TNF-alpha (16,40%; p&lt;0,002), the highest level of pro-inflammatory cytokines under stress with a frequency of every 24 hours. In HR males under these conditions, the level of IL-1beta increases (in 2.35 times; p&lt;0.001), TNF-alpha (in 8.20 times; p&lt;0.001). In exposed to stress every 72 hours in HR males, the level of TNF-alpha increases in 2.88 times (p&lt;0.002), and in LR males in 5.18 times (p&lt;0.001). At the same time, in HR females its level increases in 3.25 times (p&lt;0.01), in LR females - in 5.73 times (p&lt;0.01).Conclusion. The experiments revealed the changes of pro- and anti-inflammatory interleukins, which depends of sex, resistance to hypoxy and kinds of stress.