Levels Of Anti-inflammatory Cytokines Research Articles

The Influence of Comorbidities on Chemokine and Cytokine Profile in Obstructive Sleep Apnea Patients: Preliminary Results.

Obstructive sleep apnea (OSA) is frequently associated with a chronic inflammatory state and cardiovascular/metabolic complications. The aim of this study was to evaluate the influence of certain comorbidities on a panel of 45 chemokines and cytokines in OSA patients with special regard to their possible association with cardiovascular diseases. This cross-sectional study was performed on 61 newly diagnosed OSA patients. For the measurement of the plasma concentration of chemokines and cytokines, the magnetic bead-based multiplex assay for the Luminex® platform was used. In the patients with concomitant COPD, there were increased levels of pro-inflammatory cytokines (CCL11, CD-40 ligand) and decreased anti-inflammatory cytokine (IL-10), while in diabetes, there were increased levels of pro-inflammatory cytokines (IL-6, TRIAL). Obesity was associated with increased levels of both pro-inflammatory (IL-13) and anti-inflammatory (IL-1RA) cytokines. Hypertension was associated with increased levels of both pro-inflammatory (CCL3) and anti-inflammatory (IL-10) cytokines. Increased daytime pCO2, low mean nocturnal SaO2, and the oxygen desaturation index were associated with increased levels of pro-inflammatory cytokines (CXCL1, PDGF-AB, TNF-α, and IL-15). In OSA patients with concomitant diabetes and COPD, elevated levels of certain pro-inflammatory and decreased levels of certain anti-inflammatory cytokines may favor the persistence of a chronic inflammatory state with further consequences. Nocturnal hypoxemia, frequent episodes of desaturation, and increased daytime pCO2 are factors contributing to the chronic inflammatory state in OSA patients.

Vitamin D, VDR, and VDBP Levels Correlate with Anti-inflammatory Cytokine Profile in FMS Patients

Aim: The major target of this research is to examine whether there is any connection between the levels of vitamin D and anti-inflammatory mediators in patients with fibromyalgia syndrome (FMS). Materials and Methods: The study contains 30 FMS diagnosed and 25 healthy female individuals and the determination of FMS was made according to the standards of 2010 American College of Rheumatology (ACR). Vitamin D, vitamin D receptor (VDR), vitamin D binding protein (VDBP) levels, and anti-inflammatory cytokine (IL-4, IL-10, TGF-β) levels in the serum of patients with FMS and healthy individuals were measured using enzyme-linked immunosorbent assay (ELISA).Results: The concentrations of vitamin D, VDR, and VDBP were determined to be higher in healthy controls than in patients with FMS (p<0.001). Correlating with this, IL-4, IL-10, and TGF-β levels were measured remarkably higher in the healthy group than in the FMS patients (p<0.001). Conclusion: Low vitamin D levels may cause a decrease in anti-inflammatory cytokine levels and their immunosuppressive effect in FMS.

CYTOKINE PROFILE IN BLOOD SERUM OF INFERTILE MEN WITH CONCOMITANT PATHOLOGIES

The mechanisms of formation of male infertility are increasingly becoming immune-dependent. Immunological isolation of the testes is provided by the anatomical blood-testis barrier and the special tolerance of the immune system to antigens expressed on male gametes. For a better understanding of the immunopathogenetic mechanisms of infertility, a study of the role of various immune factors is required.
 The aim: to study the role of pro-inflammatory and anti-inflammatory cytokines in blood serum to clarify their role in spermatogenesis.
 Materials and Methods: 45 infertile men aged 22-48 were examined. They were divided into 2 groups: first group – 22 men with a systemic autoimmune disease - rheumatoid arthritis; second group – 23 somatically healthy patients with idiopathic infertility. The control group included 27 fertile healthy men aged 22-48 years. Determination of the cytokines concentration in blood serum was carried out by the immunoenzymatic method. Student's t-test was used to compare the significant difference in mean values between groups. P < 0.05 was considered significant.
 Results. Patients with autoimmune diseases (rheumatoid arthritis) had the highest rate of leukocytospermia, indicating a possible long-term inflammatory process. In patients with idiopathic infertility, oligozoospermia was diagnosed in 3 patients (13.04%), oligoasthenozoospermia in 7 patients (30.36%), asthenozoospermia in 8 patients (34.78%) and leucocytospermia in 5 patients (21.82%). In patients with rheumatoid arthritis, the concentration of IL-18 (cytokine of the IL-1 family) in the blood serum of infertile men was 1.36 times higher than that of fertile men. The level of IL-6 was 6 times higher, and the concentration of IFN-γ exceeded the norm by more than three times. The level of IL-10 was 9,4 times higher than in control group. Significant changes in the serum cytokine profile were recorded in men with idiopathic infertility. The level of pro-inflammatory cytokines increased statistically significantly: IL-18 – 1.45 times, IL-6 – 2.85 times, IFN-γ – 2.65 times. Simultaneously, the level of anti-inflammatory cytokines increased: IL-10 – 3.0 times.
 We also analyzed the ratio of serum levels of pro- and anti-inflammatory cytokines. Significant increase in ІL-10/TNF-α ratio was recorded in men with idiopathic infertility and infertile men with rheumatoid arthritis. Specifically, in men with idiopathic infertility the ІL-10/TNF-α ratio was 3.3 times higher and in patients with rheumatoid arthritis the ІL-10/TNF-α ratio was 4.1 times higher than in control group. In patients with rheumatoid arthritis the ІL-10/ІFN-γ ratio was in 3 times higher than in control group. Significant positive correlations were found in healthy fertile men: TGF-β1 – IFN-γ, IL-10 – IL-18 and IL-10 – TNF-α. In men of the control group, the synthesis of IL-18 and TNF-α was balanced by the production of IL-10. The synthesis of IFN-γ was by balanced by the production of TGF-β1.
 Conclusions. The development of infertility associated with various accompanying pathologies is related with by changes in both systemic and local immune reactivity. The pro-inflammatory cytokine profile of blood serum and a decrease in the concentration of IL-1β are observed in patients with idiopathic infertility. The largest number of deviations of immune reactivity was found in infertile men with concomitant autoimmune diseases.

Effects of Cheonggukjang (Fermented Soybean) on the Development of Colitis-Associated Colorectal Cancer in Mice.

Colorectal cancer (CRC) is the third most common type of cancer and is caused by multiple factors. Chronic inflammation, known to cause inflammatory bowel disease (IBD), is closely associated with CRC. Cheonggukjang (CJ), a traditional Korean fermented soybean, is a functional food with anti-inflammatory effects in the intestines, but its anti-cancer effects have not yet been explored. In this study, we investigated the cancer-protective effects of cheonggukjang in an azoxymethane/DSS (AOM/DSS)-induced colitis-associated colorectal cancer (CAC) mouse model. The CJ alleviated AOM/DSS-induced pathological symptoms such as colonic shortening, increased spleen weight, tumor formation, and histological changes. It also modulated pro-inflammatory and anti-inflammatory cytokine levels via the suppression of NF-κB and inflammatory mediator signaling pathways. Furthermore, the CJ improved intestinal integrity by regulating mucin-associated and tight junction proteins. In addition, it suppressed tumor growth by regulating apoptosis and proliferation. These results highlight the anti-tumor effects of CJ in an AOM/DSS-induced CAC mouse model.

Effectiveness of Hydroalcoholic Seed Extract of Securigera securidaca on Pancreatic Local Renin-Angiotensin System and Its Alternative Pathway in Streptozotocin-Induced Diabetic Animal Model.

Available data suggest inhibition of the pancreatic local-renin-angiotensin system (RAS) reduces tissue complications of diabetes. The purpose of the present study was to investigate the effect of hydroalcoholic seed extract of Securigera securidaca (S. securidaca) (HESS) on the pancreatic local-RAS and its alternative pathway. Three doses of HESS were orally administered to three groups of diabetic male Wistar rats, and the results were compared with both diabetic and healthy control groups. After 35 days of treatment, the groups were assessed for the levels of pancreatic local-RAS components, including renin, angiotensinogen, ACE, and Ang II, as well as ACE2 and Ang-(1-7) in the alternative pathway. The effect of herbal medicine treatment on tissue damage status was investigated by evaluating tissue levels of oxidative stress, proinflammatory and anti-inflammatory cytokines, and through histopathological examination of the pancreas. HESS showed a dose-dependent palliative effect on the tissue oxidative stress profile (P < 0.05) as well as the levels of pancreatic local-RAS components (P < 0.05), compared to diabetic control group. Considering the interrelationship between tissue oxidative stress and local-RAS activity, the moderating effect of HESS on this relationship could be attributed to the increase in total tissue antioxidant capacity (TAC) and pancreatic Ang-(1-7) concentration. Decrease in local-RAS activity was associated with decrease in the tissue levels of inflammatory cytokines (IL1, IL6, and TNFα) (P < 0.05) and increase in the levels of anti-inflammatory cytokine of IL-10 (P < 0.05). In addition, histological results were consistent with tissue biochemical results. Due to the reduction of local pancreatic RAS activity as well as oxidative stress and proinflammatory cytokines following treatment with HESS, S. securidaca seed can be proposed as a suitable herbal supplement in the drug-treatment of diabetes.

Influence of the Neuroprotective Properties of Quercetin on Regeneration and Functional Recovery of the Nervous System.

Quercetin is a dietary flavonoid present in vegetables, fruits, and beverages, such as onions, apples, broccoli, berries, citrus fruits, tea, and red wine. Flavonoids have antioxidant and anti-inflammatory effects, acting in the prevention of several diseases. Quercetin also has neuroprotective properties and may exert a beneficial effect on nervous tissue. In this literature review, we compiled in vivo studies that investigated the effect of quercetin on regeneration and functional recovery of the central and peripheral nervous system. In spinal cord injuries (SCI), quercetin administration favored axonal regeneration and recovery of locomotor capacity, significantly improving electrophysiological parameters. Quercetin reduced edema, neutrophil infiltration, cystic cavity formation, reactive oxygen species production, and pro-inflammatory cytokine synthesis, while favoring an increase in levels of anti-inflammatory cytokines, minimizing tissue damage in SCI models. In addition, the association of quercetin with mesenchymal stromal cells transplantation had a synergistic neuroprotective effect on spinal cord injury. Similarly, in sciatic nerve injuries, quercetin favored and accelerated sensory and motor recovery, reducing muscle atrophy. In these models, quercetin significantly inhibited oxidative stress and cell apoptosis, favoring Schwann cell proliferation and nerve fiber remyelination, thus promoting a significant increase in the number and diameter of myelinated fibers. Although there is still a lack of clinical research, in vivo studies have shown that quercetin contributed to the recovery of neurological functions, exerting a beneficial effect on the regeneration of the central and peripheral nervous system.

Investigation of relationships between serum lactate, acute phase proteins, pro/ antiinflammatory cytokine levels, and metritis formation in Holstein dairy heifers

Investigation of relationships between serum lactate, acute phase proteins, pro/ antiinflammatory cytokine levels, and metritis formation in Holstein dairy heifers

Investigation of the change in the level of pro-inflammatory, anti-inflammatory cytokine and total antioxidant in obese patients

Investigation of the change in the level of pro-inflammatory, anti-inflammatory cytokine and total antioxidant in obese patients

REVIEW OF THE NATURE OF ANTI/INFLAMMATORY AND PRO-INFLAMMATORY CYTOKINE REGULATION IN DIFFERENT PERIODS OF PLASMA CELL MYELOMA NATURAL HISTORY IN THE CHORNOBYL NPP ACCIDENT SURVIVORS.

identify the nature of anti-inflammatory and pro-inflammatory cytokine regulation in different periods of plasma cell myeloma (PCM) natural history with evaluation of its role as a prognostic criterion for the disease course in the Chornobyl NPP (ChNPP) accident survivors. Levels of pro-inflammatory (IL-6, TNF-α) and anti-inflammatory (IL-10) cytokines both with their relationship were studied in the stage I-II and stage III PCM patients (n = 74) in different periods of the disease natural history i.e. remission/stabilization and progression. Study groups included the ChNPP accident survivors (n = 35) and non-irradiated subjects (n = 39). Immunoenzymatic method was applied using the Vector-Best CJSC commercial kits. There was a unidirectional increase in the levels of IL-6, TNF-α, and IL-10 in irradiated persons, and an elevation of IL-6 and TNF-α concentration but with a decreased level of IL-10 in non-irradiated subjects compared to control at the time of PCM diagnosis. Period of the disease remission/stabilization in PCM stage I-II patients featured a decrease in IL-6 concentration regardless of the exposure to ionizing radiation, while TNF-α content remained at the level of the control group. There was a significant increase in IL-6 concentration in both study groups during the disease relapse, while TNF-α level remained unchanged compared to stabilization phase of the disease. According to the obtained data a certain contribution of radiation exposure to the PCM pathogenesis as a possible predictor of the exacerbated disease course cannon be excluded. Determining the serum level of pro-inflammatory and anti-inflammatory cytokines (IL-6, TNF-α and IL-10 respectively) provides advancement in assessment of the PCM course and predict the effectiveness of administration of therapy protocols.

Features of inflammatory reactions in patients with juvenile depression with a clinically high risk of psychosis

To determine the levels of pro-inflammatory and anti-inflammatory cytokines and inflammatory markers such as C-reactive protein, leukocyte elastase, α1-proteinase inhibitor, autoantibodies to neuroantigens in the blood of patients with adolescent depression with clinical high risk for psychosis (CHR-P) and to study the relation of these biological markers to the features of psychopathological symptomatology of the patients. Eighty young adults, aged 16-24 years, with the first depressive episode (F32.1-2, F32.38, F32.8) were studied. Based on the presence of attenuated positive symptoms in the structure of depression, all patients were divided into two groups: with CHR-P (clinical group, n=58) and without CHR-P (comparative group, n=22). The HDRS-21, SOPS, and SANS were used for psychometric assessment of the patients. Serum levels of cytokines TNF-α, IL-6, IL-8, IL-10, and concentration of C-reactive protein (CRP) were determined. Leukocyte elastase (LE) activity, α1-proteinase inhibitor (α1-PI) activity, and plasma levels of autoantibodies to S100B protein and myelin basic protein (MBP) were assessed. Both groups of patients were characterized by the high levels of inflammation as assessed by LE (250.5 (226.2-280.8) nmol/min·ml vs 248.3 (226.8-284.5) nmol/min·ml) and α1-PI activity (44.4 (37.5-50.1) IE/ml vs 45.2 (36.4-49.9) IE/ml). Higher levels (p<0.05) of IL-6 (1.22 (0.64-2.2) pg/ml), CRP (0.93 (0.18-3.18) mg/l), and TNF-α/IL-10 (0.34 (0.2-0.47)) were detected in the group with CHR-P. This group was also characterized by higher levels of antibodies to the S100B protein 0.78 (0.69-0.84 units of opt.density) compared with the group without CRH-P (p<0.05). In each clinical group, different correlations between clinical, psychometric and biological parameters were revealed. The results confirm the involvement of inflammation in the development of depression in youth and indicate a different role of the inflammatory markers analyzed in the formation of CHR-P. The differences in the spectrum of inflammatory markers in depressed patients suggest a more pronounced pro-inflammatory potential in the group with CHR-P.

PREDICTION OF THE DYSBIOSIS DEVELOPMENT RISK ACCORDING TO HUMORAL IMMUNITY INDICATORS

Diseases associated with bacterial vaginosis lead to chronic inflammatory processes of the internal genitals, the development of adhesions of the pelvic organs, infertility, spontaneous abortion at different times, as well as the development of malignant neoplasms. Vaginal microflora is an indicator of a woman’s health, which can form changing in hormonal and immunological status during various pathological conditions. The aim of the study was to create a system for prediction of the dysbiosis development according to the levels of nonspecific humoral factor of immune defense. Materials and methods. The study was performed in 298 women aged 16 to 64 years, 53 of whom were diagnosed with normocenosis, and 245 have dysbiosis. Women were divided into 3 groups according to age. Regression analysis was used. Research results and their discussion. Our previous research have shown a correlation between increased levels of anti-inflammatory cytokines in the blood and vaginal secretions with the stage of dysbiosis. A logistic regression model was constructed during the study, which showed that the risk of developing dysbiosis in terms of normobiota increases with increasing levels of interleukin 2 in the blood, tumor necrosis factor α. Significant features of the three-factor model for predicting the risk of developing dysbiosis (IL2, IL4 and TNFα) were selected by the method of genetic algorithm. The levels of these indicators in the blood were related to the severity of dysbiosis according to the results of discriminant analysis. Conclusions. Thus, a linear neural network model was developed for determination of dysbiosis severity according to the levels of nonspecific humoral factors of immune defense such as the C4 component of the complement system and γ-interferon in vaginal secretions, as well as the amount of circulating immune complexes and tumor necrosis factor α in the blood. Kappa Cohen’s agreement for this model on the training set was 0.87 (95% CI 0.82-0.91), and on the confirmatory set was 0.89 (95% CI 0.77-1.00). These indicators show the adequacy of the constructed model. The interface of the expert system for the dysbiosis severity prediction has been created. Key words: normobiota, bacterial vaginosis, linear neural network model for determination of the dysbiosis severity, humoral factor of immune defense.

Adipose-derived mesenchymal stem cells in emphysema: Comparison of inflammatory markers changes in response to intratracheal and systemic delivery method

Cytokines are the most important inflammatory mediators and are well-known as the main cause of emphysema. Adipose-derived stem cells (ADSCs) as a cell-based treatment strategy could play a pivotal role in lung regeneration through anti-inflammatory and paracrine properties. Accordingly, the aim of this study was to the comparison of inflammation markers' improvement in response to the intratracheal and systemic delivery method of adipose-derived mesenchymal stem cells in emphysema. Forty-eight rats were divided into five groups including Control, Elastase (25 IU/kg, Intratracheal, at day first and 10th), Elastase+PBS, Intratracheal cell therapy (1 ×107, at day 28th), and Systemic cell therapy groups (1 ×107, Jugular vein, at day 28th). After 3 weeks, the blood gas analysis (PO2, PCO2 and pH), fibrinogen level, and C-reactive protein (CRP) concentrations were measured in all groups. In addition, inflammatory genes expression, and concentration levels of pro and anti-inflammatory cytokines (IL-6, IL-17, TNF-α, and TGF-β,) were evaluated using Real-time PCR and Elisa kits, respectively. The statistical analysis of our data shows that local administration leads to more significant treatment efficacy with decreased inflammation parameters such as WBC count and pro-inflammatory cytokines in comparison with systemic treatment. Besides, these results were approved by more reduction of CRP and fibrinogen concentration levels in blood samples of intra-tracheal AMSCs-treated rats compare with the systemic group. Moreover, the improvement in histopathology indexes of the local administrated group was significantly better than the systemic group. Accordingly, the obtained results suggest local administration as the most efficacious route for mesenchymal stem cells delivery in patients with emphysema.

Immunopathological Responses to the Bovine Mastitis Associated with Staphylococcus Species Infection

Bovine mastitis is a disease that concerns animals' welfare and increases the economic production losses. Bacterial agents such as Staphylococcus species are the main causative agent of bovine mastitis. This bacterial agent expresses some inflammatory cytokines that might enhance the cell-mediated, which may promote the pathogenesis of mastitis. The objective of the current study was to investigate the bovine innate immune response circulating levels of pro-inflammatory and anti-inflammatory cytokines. A total of 10 mL of milk specimens were collected randomly from 100 clinically mastitic cows, and another 20 clinically healthy cows were considered as a control group for the California Mastitis test. The microbiological cultures of milk specimens were performed. The interleukins (ILs)that involved IL-4, IL-6, and IL-10 were detected using the ELISA test for the evaluation of the pro-inflammatory bovine mastitis pathophysiology. The results of this study showed that Staphylococcus aureus detection was in 31.2% of mastitic milk and 8.7% of non-mastitic milk specimens; and the coagulase-negative Staphylococcus was detected in 14.8% and 18.7% in the mastitic and non-mastitic milk specimens, respectively. The IL-6 level was shown significantly higher (P&lt;0.05)in the specimens of mastitic milk (194±12.8 pg/mL) compared to the non-mastitic milk (31±2.9 pg/mL). In conclusion, the elevated level of expression of IL-6 cytokine in the milk of cows with mastitis suggested that IL-6 might be used as a potentially suitable biomarker for early bovine mastitis diagnosis

Psidium cattleianum fruit extract prevents systemic alterations in an animal model of type 2 diabetes mellitus: comparison with metformin effects

Objective: In this study, we aimed to determine the role of Psidium cattleianum extract (PCE) and compare its effects with those of metformin (Met) in an animal model with type 2 diabetes mellitus (T2DM). Methods: T2DM was induced in rats using a high-fat diet (HFD), followed by a single dose of streptozotocin (STZ). Met and PCE were administered intragastrically once a day throughout the experiment, and their effects on biochemical, inflammatory, oxidative, and histological parameters were evaluated. Results: Met and PCE prevented the increase in serum levels of glucose, total cholesterol (TC), triacylglycerol (TG), very low-density lipoprotein (VLDL) and interleukin-6 (IL-6) induced by T2DM, and restored redox homeostasis in the liver and brain. Met increased the serum levels of anti-inflammatory cytokine and interleukin-10 (IL-10). Furthermore, both treatments restored the liver and pancreas from marked cellular disorganisation, vacuolisation, and necrosis, with PCE being more effective than Met in recovering histological changes. Conclusion: PCE is a promising agent for the prevention of T2DM complications.

CYTOKINE-MEDIATED REACTIONS IN THE PATHOGENESIS OF EXPERIMENTAL PERIODONTITIS

Determining cytokinemia role in the destructive processes of the periodontal complex gives new opportunities to the development and subsequent implementation of practical methods for chronic periodontitis diagnosis, justifies including pathogenetic drugs that inhibit the secretion of pro-inflammatory mediators in treatment regimens.&#x0D; The aim of the study is to evaluate the dynamics of cytokine profile indicators and identify their correlation with the local status of periodontal tissues in animals with experimental periodontitis.&#x0D; Materials and methods. The study enrolled 65 white outbred rats weighing 180±20 g. The authors reproduced the model of experimental periodontitis according to K.D. Shkolnaya, V.G. Atrushkevich method (patent RU No. 2625295, December 07, 2017). The cytokine profile was assessed by pro-inflammatory and anti-inflammatory cytokine levels, determined by enzyme-linked immunosorbent assay, Bender MedSystems reagent kit. Local status of periodontal tissues was assessed according to the degrees of gingival hemorrhage, dental mobility and depth of periodontal pockets with a button-shaped and modified periodontal probes.&#x0D; Results. During the experimental periodontitis modeling, a high level of cytokinemia was determined. It destructively effects the periodontal connective tissue matrix, which was confirmed by an increase in the depth of periodontal pockets, gingival hemorrhage and dental mobility. A strong correlation between a high level of cytokinemia and local destructive changes in periodontal tissues was determined. This fact emphasized the conjugation of these pathophysiological mechanisms.&#x0D; Conclusion. Defined disorders of physiological balance in the cytokine balance necessitate the use of pathogenic drugs, as they have an inhibitory effect on the synthesis of pro-inflammatory cytokines and prevent further destruction of the periodontal complex. Changes in the cytokine profile indicate inflammation process, and a decrease in the level of cytokinemia indicate the resolution of infection and can be considered a criterion for the effective treatment.

Resolvin D5 (RvD5) Reduces Renal Damage Caused by LPS Endotoxemia in Female Mice.

In self-revolving gram-negative Escherichia coli infection, Resolvin D5 (RvD5) was found to enhance bacteria phagocytosis and reduce the production of inflammatory mediators, contributing to the resolution of infection. LPS (lipopolysaccharide) is a gram-negative bacterial structure product which activates the immune system and, at high doses, leads to endotoxemia. To our knowledge, the effect of RvD5 against LPS endotoxemia has not been investigated to date. Female Swiss mice received an i.p. treatment with RvD5 (0.1, 1 or 10 ng/animal). After 1 h, they were stimulated with LPS (10 mg/kg, i.v.), and samples were collected after additional 6 h. The resulting data demonstrated that RvD5 protected the kidneys (urea and creatinine serum levels) from tissue injury. These effects were related to an improvement in histopathological parameters and a reduction of enzymatic markers of leukocyte infiltration, pro-inflammatory cytokine (IL-1β, TNF-α, and IL-6) production, and oxidative stress. Antioxidant markers were also increased by RvD5, but IL-10 (an anti-inflammatory cytokine) levels were unaltered. We also observed that RvD5 reduced the infiltration of CD45+ hematopoietic cells into the kidneys, reduced the activation of NFκB and promoted the Nrf2 pathway by reducing Keap-1 levels. Our data indicate that RvD5 may be a therapeutic possibility to reduce kidney lesions in LPS endotoxemia.

Huperzine-A Improved Animal Behavior in Cuprizone-Induced Mouse Model by Alleviating Demyelination and Neuroinflammation.

Huperzine A (HupA) is a natural acetylcholinesterase inhibitor (AChEI) with the advantages of high efficiency, selectivity as well as reversibility and can exhibit significant therapeutic effects against certain neurodegenerative diseases. It is also beneficial in reducing the neurological impairment and neuroinflammation of experimental autoimmune encephalomyelitis (EAE), a classic model for multiple sclerosis (MS). However, whether HupA can directly regulate oligodendrocyte differentiation and maturation and promote remyelination has not been investigated previously. In this study, we have analyzed the potential protective effects of HupA on the demylination model of MS induced by cuprizone (CPZ). It was found that HupA significantly attenuated anxiety-like behavior, as well as augmented motor and cognitive functions in CPZ mice. It also decreased demyelination and axonal injury in CPZ mice. Moreover, in CPZ mice, HupA increased mRNA levels of the various anti-inflammatory cytokines (Arg1, CD206) while reducing the levels of different pro-inflammatory cytokines (iNOS, IL-1β, IL-18, CD16, and TNF-α). Mecamylamine, a nicotinic acetylcholinergic receptor antagonist, could effectively reverse the effects of HupA. Therefore, we concluded that HupA primarily exerts its therapeutic effects on multiple sclerosis through alleviating demyelination and neuroinflammation.

714 PLEIOTROPIC EFFECTS OF ANTICOAGULANT THERAPIES: IS THERE A DIFFERENCE BETWEEN AVK AND DOAC?

Abstract Background Atrial fibrillation (AF) is the most common supraventricular arrhythmia. Emerging evidence suggests a significant role of inflammation in the pathogenesis and in the maintenance of AF. We hypothesize a different role of anticoagulant therapy (AVK vs. DOACs) in reducing the levels of inflammatory biomarkers in AF. Methods The Strat-AF study is an observational, prospective, single-center hospital-based study enrolling patients with atrial fibrillation, aged 65 years or older, and with no contraindications to undergo magnetic resonance imaging. Recruited patients are evaluated by means of a comprehensive protocol, with clinical and circulating biomarkers assessment. One of the main outcomes is the evaluation of the grade of inflammation in patients treated with AVK vs. DOACs. In order to evaluate the grade of inflammation, we calculated the ratios between pro- and anti-inflammatory cytokines (IL6/IL4, IL6/IL10, TNF-alpha/IL4, TNF-alpha/IL10). The pro-/anti-inflammatory ratios were divided into tertiles and were used to calculate a score of inflammation. Patients with ratios in the third tertile were assigned as patients with an elevated grade of inflammation not balanced by anti-inflammatory cytokines; patients with ratios in the other tertiles were assigned as patients with a low level of inflammation. Starting from September 2017, 191 patients (mean age 78.1±6.7, range 65-97; 65.3% males) were enrolled. 56 patients (29.3%) were on vitamin K antagonists, and 135 (70.7%) were on direct oral anticoagulants. Results Patients treated with DOACS had higher ratio values than patients treated with AVK [IL6/IL4: 0.15 (0.07-0.35) vs 0.05 (0.03-0.25), p=0.001; IL6/IL10: 0.70 (0.28-5.49) vs 0.54 (0.18-1.42), p=0.090; TNF-alpha/IL4: 0.16 (0.12-0.31) vs 0.13 (0.08-0.31), p= 0.055; TNF-apha/IL10: 0.97 (0.25-5.23) vs 0.75 (0.51-2.62), p=0.105]. According to pro-anti-inflammatory ratio tertiles, 28/135 DOAC patients (20.7%) had an elevated grade of inflammation not balanced by anti-inflammatory cytokines, whereas in AVK group only 5.4% (3/53) were classified as patients with high levels of inflammation (p=0.009). At multivariate logistic regression analysis, adjusted for age, sex, CHA2DS2-VASc, HAS-BLED, AVK treatment resulted an independent and protective predictor for having a high grade of inflammation not balanced by anti-inflammatory cytokine levels [OR=0.27 (0.08-0.97), p=0.045]. Conclusions These result from Strat-AF study may be an essential step towards the exploration of the role and the contribute of anticoagulant therapy in reducing inflammation-related biomarkers in AF patients. Inflammation has also been associated with endothelial dysfunction, coagulation cascade activation and thrombogenesis. Thus, inflammation may contribute to both the occurrence/maintenance of AF and its thromboembolic complications. These results might sustain the incorporation of such new markers in the existing stroke prediction schemes by the demonstration of a greater incremental value in predicting

THE CYTOKINE SYSTEM IN THE SECOND HALF OF PHYSIOLOGICAL PREGNANCY AND DURING LABOR

A study was conducted to study the level of anti-inflammatory (IL-4) and pro-inflammatory (IL-1β, IL-6, IFNγ, TNFα) cytokines in 28 women with physiological pregnancy in the third trimester and in 23 women with incipient labor. It was found that in the prenatal period, the level of IL-1β and IL-8 increases sharply, and the level of IL-4 decreases sharply. The levels of IL-6 and TNFα are also slightly elevated. Therefore, the study of the level of pro- and anti-inflammatory cytokines in parturient women with a physiologically proceeding pregnancy is of great interest, since it is this mechanism of changes in the level of cytokines during incipient labor activity that is observed in a pathologically proceeding pregnancy with the threat of premature birth.

Effects of Ovine Monocyte-Derived Macrophage Infection by Recently Isolated Toxoplasma gondii Strains Showing Different Phenotypic Traits.

Ovine toxoplasmosis is one the most relevant reproductive diseases in sheep. The genetic variability among different Toxoplasma gondii isolates is known to be related to different degrees of virulence in mice and humans, but little is known regarding its potential effects in sheep. The aim of this study was to investigate the effect of genetic variability (types II (ToxoDB #1 and #3) and III (#2)) of six recently isolated strains that showed different phenotypic traits both in a normalized mouse model and in ovine trophoblasts, in ovine monocyte-derived macrophages and the subsequent transcript expression of cytokines and iNOS (inducible nitric oxide synthase). The type III isolate (TgShSp24) showed the highest rate of internalization, followed by the type II clonal isolate (TgShSp2), while the type II PRU isolates (TgShSp1, TgShSp3, TgShSp11 and TgShSp16) showed the lowest rates. The type II PRU strains, isolated from abortions, exhibited higher levels of anti-inflammatory cytokines and iNOS than those obtained from the myocardium of chronically infected sheep (type II PRU strains and type III), which had higher levels of pro-inflammatory cytokines. The present results show the existence of significant intra- and inter-genotypic differences in the parasite-macrophage relationship that need to be confirmed in in vivo experiments.