Anti-inflammatory Cytokine Concentrations Research Articles

Immune alterations in children with autism spectrum disorders

Autism spectrum disorders (ASD) are a heterogeneous group of mental and nervous system disorders. Patients with ASD are characterized by communication and cognitive impairments and obsessive behavior. The pathogenesis and etiology of ASD are still unclear. According to the literature, patients suffering from ASD have not only mental, but also somatic disorders, including changes in the immune system. The aim of this work was to study the concentration of cytokines in the blood plasma of children with ASD and the level of expression of proinflammatory genes in peripheral blood mononuclear cells. The clinical group included 71 children aged 4-12 years with a diagnosis of ASD (F84.02). Patients scored more than 36 on the Childhood Autism Rating Scale (CARS). The control sample included 27 apparently healthy children of the same age. The following methods were used in this study: isolation of mononuclear cells from heparinized peripheral blood, Ficoll-Verografin density gradient centrifugation, evaluation of cytokine blocks using commercially available enzyme immunoassay kits, isolation of random total RNA, reverse transcription using hexaprimers, and real-time polymerase chain reaction using intercalating dye SYBR Green. The concentration of proinflammatory cytokines IL-1β, IL-8, and IL-17A in the peripheral blood plasma of children with ASD was statistically significantly increased compared to the control sample. Moreover, the concentration of the anti-inflammatory cytokine IL-10 in patients with ASD was 3.6 times lower compared to the control sample (p 0.001). The level of expression of the NF-κB1, IL1β, IL8 and TNFα genes at the RNA level in peripheral blood mononuclear cells was increased by 2.8, 2.5, 4.8 and 4.2 times in patients with ASD compared to the control sample (all p 0.01). The results obtained indicate an increase in the concentration of proinflammatory cytokines (IL-1β, IL-8, IL-17A) in the blood plasma and a decrease in the concentration of anti-inflammatory cytokines (IL-10) in patients with ASD compared to the control sequence.

Synthesis of cytokines during physiological pregnancy

The article is devoted to the study of the level of pro- and anti-inflammatory cytokines in women with a physiological pregnancy, which is of great importance in obstetrics. Studying the synthesis of cytokines makes it possible to identify disturbances in the course of pregnancy, which is of great practical importance. The authors conducted a study of the level of cytokines in women with physiological pregnancy. Purpose of the study: to study the serum concentration of pro-inflammatory (IL-1β, IL-6, TNFα, IFNγ) and anti-inflammatory (IL-4, IL-10) cytokines in the dynamics of physiological pregnancy. The level of serum cytokines was studied in 94 women with a physiologically progressing pregnancy, who were registered with advisory clinics No. 14, No. 26, and No. 28 in Bukhara. The age of pregnant women ranged from 21 to 37 years, averaging 26.3±1.5 years. When compiling groups by trimester of pregnancy, it was revealed that: 35 women were in the first trimester of pregnancy; in 31 – the second trimester; and in 28 women – the third trimester of pregnancy. The control group consisted of 30 practically healthy non-pregnant women who were comparable in age. The levels of cytokines 1β, IL-6, TNFα, IFNγ, IL-4, and IL-10 was determined in peripheral blood serum using a set of reagents produced by Cytokin LLC (St. Petersburg, Russia) using the ELISA method according to the manufacturer’s instructions. Statistical processing of the obtained results was carried out using Student’s t-test using the standard Windows 2000 statistical software package. An increase in the level of proinflammatory cytokines (IFNγ, TNFα) was detected in the early stages of gestation compared with data from healthy non-pregnant women, which persisted in the second half of pregnancy against the background of an increase in anti-inflammatory cytokines (IL-4, IL-10). In the third trimester of pregnancy, a further increase in the serum level of pro-inflammatory cytokines (IL-1β, TNFα, IFNγ) was observed. The results of the studies indicate that at the level of the cytokine network there are mechanisms of fetoprotection, the violation of which can be the cause of pregnancy pathology.

Inflammation and lipoperoxidation in mucopolysaccharidoses type II patients at diagnosis and post-hematopoietic stem cell transplantation

IntroductionMucopolysaccharidosis type II (MPS II) is caused by deficiency of the enzyme iduronate-2-sulfatase; one possible therapy for MPS II is hematopoietic stem cell transplantation (HSCT). It is established that there is excessive production of reactive species in MPS II patients, which can trigger several processes, such as the inflammatory cascade. ObjectivesOur aim was to outline an inflammatory profile and lipoperoxidation of MPS II patients for a better understanding of disease and possible benefits that HSCT can bring in these processes. Materials and MethodsWe investigate oxidative damage to lipids by 15-F2t-isoprostane urinary concentrations and plasma pro-and anti-inflammatory cytokine concentrations in MPS II patients at diagnosis, MPS II post-HSCT patients, and controls. ResultsInterleukin (IL)-1β and IL-17a concentrations were significantly increased and a tendency toward increased IL-6 production in the diagnosis group was verified. We found significant decrease in IL-4 and increase in 15-F2t-isoprostane concentrations in the diagnosis group, while IL-1β, IL-6, IL-17a and 15-F2t-isoprostane concentrations were similar between control and post-HSCT groups. ConclusionsOur study demonstrated that MPS II patients at diagnosis are in a pro-inflammatory state, bringing a novel result showing increased production of IL-17a, an osteoclastogenic cytokine, as well as demonstrating that these patients have oxidative damage to lipids. Furthermore, evidence suggests that HSCT can reduce inflammation and lipoperoxidation in MPS II patients.

Oral mucositis management with photobiomodulation, Bidens pilosa L. (Asteraceae) and Curcuma longa L. (Zingiberaceae), the FITOPROT herbal medicine, and its influence on inflammatory cytokine levels: a randomized clinical trial.

This randomized clinical trial aimed to compare the effects of a mucoadhesive formula, containing curcuminoids from Curcuma longa L. and glycerinated extract of Bidens pilosa L. (FITOPROT), associated with photobiomodulation (PBM), and of PBM exclusively, on the incidence of oral mucositis (OM)-induced by radiotherapy (RT) in the head and neck region, and the salivary expression of inflammatory cytokines, in patients with head neck cancer. Patients were randomly assigned into two intervention groups-FITOPROT + PBM (n = 25) or PBM (n = 27). PBM protocol comprised a wavelength of 660nm, 25 mW, 0.25J/point, and daily irradiation from the first until the last day of RT. FITOPROT was gargled twice a day. All patients underwent a preventive oral care program throughout the study. OM degree, salivary concentration of nitrite, and inflammatory (IL-1, TNFα, IL-6, IL-8, and IL-12p70), and anti-inflammatory (IL-10) cytokines were assessed at baseline, and at the 7th, 14th, 21st, and 30th RT sessions. There were no differences in the OM degree between groups, but the RT dose significantly affected the OM. The RT significantly affected the salivary nitrite, TNFα, IL-1β, and IL-10 concentrations. FITOPROT associated with PBM showed limited effects on preventing the incidence of severe OM compared to PBM alone. However, FITOPROT + PBM may be associated with nitrite and cytokine balance, which may contribute to the occurrence of fewer cases of severe OM. Brazilian Clinical Trials database (ReBEC; RBR-9vddmr), registered UTN code: U1111-1193-2066, registered in August 8th, 2017.

Diagnostic significance of interleukin levels in blood serum in premenopausal women with chronic endometritis and normal weight or overweight

Background. Chronic endometritis (CE) is an inflammatory hysteropathy causing miscarriage and infertility. High invasiveness of the main method of CE diagnosis and vague clinical picture necessitate the need for the development of less invasive approaches to establish the presence of this disease.The aim of the study. To establish a significant association of the concentration of pro- and anti-inflammatory interleukins in the blood serum with the presence of chronic endometritis in premenopausal women without concomitant endocrine diseases.Materials and methods. This re-analysis of the data is based on the results of a cross-sectional study conducted between May 2017 and December 2019 which included 198 premenopausal women. In all participants, body weight and height were measured with the calculation of the body mass index, the concentration of Creactive protein, pro- and anti-inflammatory cytokines in the blood serum was determined, and a pipelle biopsy was performed to determine the CD138 expression in the endometrial stroma. Non-parametric methods, as well as ROC analysis, were used for statistical analysis.Results. 86 women were included in the re-analysis of the data, 37 of them had a confirmed diagnosis of chronic endometritis. Statistically significantly higher values of interleukin 1 (IL-1) concentration (p = 0.0028) and IL-1/tumor necrosis factor α ratio (p < 0.001) were determined in women with CE and normal body weight; threshold values of these parameters were ≥ 1.35 pg/ml (sensitivity 75 %, specificity 83 %; 95% confidence interval (95% CI): 0.88–2.15) and ≥ 1.03 (sensitivity 85 %, specificity 78 %; 95% CI: 0.81–1.27) respectively. Such a relationship was not revealed in women with overweight.Conclusions. The obtained results can be the basis for conducting a larger-scale study with determining the concentration of cytokines not only in the blood serum, but also in the endometrium of women with CE, which will allow the development of a minimally invasive method for determining the risk of the presence of chronic endometritis in premenopausal women.

Cytokine Profiling in Cerebrospinal Fluid of Patients with Newly Diagnosed Relapsing-Remitting Multiple Sclerosis (RRMS): Associations between Inflammatory Biomarkers and Disease Activity.

Cytokines regulate immune responses and are crucial to MS pathogenesis. This study evaluated pro-inflammatory and anti-inflammatory cytokine concentrations in the CSF of de novo diagnosed RRMS patients compared to healthy controls. We assessed cytokine levels in the CSF of 118 de novo diagnosed RRMS patients and 112 controls, analyzing relationships with time from symptom onset to diagnosis, MRI lesions, and serum vitamin D levels. Elevated levels of IL-2, IL-4, IL-6, IL-13, FGF-basic, and GM-CSF, and lower levels of IL-1β, IL-1RA, IL-5, IL-7, IL-9, IL-10, IL-12p70, IL-15, G-CSF, PDGF-bb, and VEGF were observed in RRMS patients compared to controls. IL-2, IL-4, IL-12p70, PDGF, G-CSF, GM-CSF, and FGF-basic levels increased over time, while IL-10 decreased. IL-1β, IL-1RA, IL-6, TNF-α, and PDGF-bb levels negatively correlated with serum vitamin D. TNF-α levels positively correlated with post-contrast-enhancing brain lesions. IL-15 levels negatively correlated with T2 and Gd(+) lesions in C-spine MRI, while TNF-α, PDGF-bb, and FGF-basic correlated positively with T2 lesions in C-spine MRI. IL-6 levels positively correlated with post-contrast-enhancing lesions in Th-spine MRI. Distinct cytokine profiles in the CSF of de novo diagnosed MS patients provide insights into MS pathogenesis and guide immunomodulatory therapy strategies.

Burkholderia cepacia in cystic fibrosis children and adolescents: overall survival and immune alterations.

In current literature there are only scarce data on the host inflammatory response during Burkholderia cepacia complex (Bcc) persistence. The primary objective of the present research was to carry out cross-sectional analyses of biomarkers and evaluate disease progression in cystic fibrosis (CF) patients with chronic Bcc infection and pathogen-free ones. The secondary aim was to assess prospectively overall survival of the study participants during up to 8 years of follow-up. The study included 116 paediatric patients with CF; 47 CF patients were chronically infected with Bcc, and 69 individuals were Bcc free. Plasma and sputum biomarkers (neutrophil elastase, MMP-8, MMP-9, MMP-12, IL-2, IL-4, IL-6, IL-8, IL-10, IL-18, IL-22, IL-23, IL-17, IFN-γ, TGFβ1, TNF-α) were analysed using commercially available kits. Besides, inhibitory effect of dexamethasone on proliferative response of PHA-stimulated peripheral blood lymphocytes had been assessed. Bcc infected patients did not differ from Bcc free ones in demographic and clinical parameters, but demonstrated an increased rate of glucose metabolism disturbances and survival disadvantage during prolong follow-up period. Biomarkers analyses revealed elevated TNF-α and reduced IL-17F levels in sputum samples of Bcc infected patients. These patients also demonstrated improvement of peripheral blood lymphocyte sensitivity to steroid treatment and reduction in plasma pro-inflammatory (IL-17F and IL-18) and anti-inflammatory (TGFβ1 and IL-10) cytokine concentrations. Reduction in IL-17F levels may have several important consequences including increase in steroid sensitivity and glycemic control disturbances. Further investigations are needed to clarify the role of IL-17 cytokines in CF complication development. Low plasma TGFβ1 and IL-10 levels in Bcc infected group may be a sign of subverted activity of regulatory T cells. Such immune alterations may be one of the factors contributing to the development of the cepacia syndrome.

Poster 242: Exploring the Correlation Between Synovial Fluid Cytokine Profiles and Meniscal Treatment Outcomes

Objectives: Meniscal tears are a common injury and have been shown to contribute to the development of posttraumatic osteoarthritis (PTOA) in affected individuals. Research indicates that meniscal repair yields more favorable outcomes compared to partial and subtotal meniscectomies, with a protective effect against the incidence of PTOA. The aim of this study was to investigate whether a distinct synovial fluid profile was associated with meniscal injuries amenable to repair, thereby shedding light on potential biomarkers or factors that may predict treatment selection and improve preoperative patient counseling. Methods: Patients were prospectively recruited between January 2011 and the present and were enrolled on the day of surgery. The operative knee was aspirated aseptically, following skin preparation and patient draping. The synovial fluid was analyzed to determine concentrations of biomarkers. Patients with meniscal injuries and complete synovial fluid results for all 10 cytokines were included: Regulation on Activation Normal T Cell Expressed and Secreted (RANTES), Interleukin 6 (IL-6), Monocyte Chemoattractant Protein 1 (MCP-1), Macrophage Inflammatory Protein-1 beta (MIP-1b), Vascular Endothelial Growth Factor (VEGF), Tissue Inhibitor Matrix Metalloproteinase 1 and 2 (TIMP-1, TIMP-2), Interleukin 1 Receptor Antagonist (IL1-RA), and Matrix Metalloproteinase 3 (MMP-3). Elite athletes were excluded from analysis. Hierarchical clustering was performed on the biomarker concentrations to identify two distinct clusters. The percentage of patients with meniscal tears amenable to repair and synovial fluid levels were compared between the identified clusters using the chi-square test and t test. Results: A total of 183 patients were included, of which 46 underwent a meniscal repair. The average body mass index (BMI) was 27.95 ± 5.63, and the mean age at the time of surgery was 38.48 ± 10.19. The cohort consisted of 58.5% male patients. There was a significantly higher proportion of patients who experienced a bucket handle tear in those who underwent a repair procedure versus a meniscectomy (21.7% vs. 5.1%, p = 0.002). There was no other difference in meniscal tear patterns between the groups (posterior horn, p = 0.062; anterior horn, p = 0.34; radial, p = 0.17; body, p = 1). Through hierarchical clustering, the analysis identified two distinct clusters: cluster 1, comprising 115 patients, and cluster 2, consisting of 68 patients. There were no significant differences in age (38.51 vs. 38.43, p = 0.96), sex (55.7% vs. 63.2% male, p = 0.11) or BMI (27.85 vs. 28.13, p = 0.75) between the 2 clusters. Cluster 1 exhibited a higher rate of meniscal tears amenable to repair as compared to cluster 2 (24.3% vs. 8.8%, p = 0.016). Furthermore, cluster 1 had a higher percentage of reported cartilage injuries (11.3% vs. 1.5%, p = 0.033). Additionally, cluster 1 showed higher log-transformed concentrations of MIP-1b (3.56 vs. 3.18, p = 0.002), TIMP-1 (13.06 vs. 10.08, p < 0.001), and TIMP-2 (10.56 vs. 7.20, p < 0.001), while demonstrating lower concentrations of RANTES (4.08 vs. 4.86, p = 0.008) compared to cluster 2. Stepwise logistic regression was performed to identify the cytokines that are associated with the likelihood of a repairable meniscal tear, controlling for age, sex, BMI, cartilage lesion grade, and meniscal pathology. The resulting model included sex, posterior horn tear, handle tear, radial tear, body tear and bucket handle tear, which is a known confounder for meniscal repair, and revealed statistically significant relationships between certain biomarkers and the odds of encountering a repairable tear. Specifically, MCP-1, TIMP-2, and MMP-3 were significantly associated with the odds of a repairable meniscus. The amenability of meniscal repair decreased by 76% (95% CI: 0.64 - .69, p = 0.017), for each unit increase of pre-operative levels of MCP-1, increased by 74% for TIMP-2 (95% CI: 1.06 – 3.00, p = 0.032), and increased by 88% for MMP-3 (95% CI: 1.18 – 3.34, p = 0.014). Conclusions: The study findings provide insights into the relationship between synovial fluid biomarkers and meniscal tear patterns. The analysis revealed a distinct group of patients (cluster 1) characterized by higher concentrations of anti-inflammatory cytokines (TIMP-1 and TIMP-2) and lower levels of the pro-inflammatory cytokine RANTES, suggesting a potential correlation between a more favorable cytokine profile and the feasibility of meniscal repair. The elevated concentrations of TIMP-1 and TIMP-2 in cluster 1 suggest an enhanced ability to regulate matrix metalloproteinases (MMPs), resulting in reduced degradation of the extracellular matrix and a potentially more favorable environment for meniscal repair. These results provide evidence suggesting that the synovial fluid cytokine profile may represent the likelihood that a meniscal tear is repairable. This knowledge has the potential to inform treatment decisions and enhance preoperative patient counseling by identifying individuals who are more likely to have meniscal pathology amenable to repair as opposed to necessitating partial or subtotal meniscectomy.

Lactobacillus Plantarum intake mitigates neuropathic pain behavior via enhancing macrophage M2 polarization in a rat model of peripheral neuropathy

Pro-inflammatory macrophages (M1-polarized) play a crucial role in neuroinflammation and neuropathic pain following nerve injury. Redirecting macrophage polarization toward anti-inflammatory (M2-polarized) phenotypes offers a promising therapeutic strategy. Recognized for their anti-inflammatory and immunomodulatory properties, probiotics are becoming a focal point of research. This study investigated the effects of Lactobacillus plantarum on macrophage polarization, nerve protection, and neuropathic pain behavior following chronic constriction injury (CCI) of the median nerve. Rats received daily oral doses of L. plantarum for 28 days before and 14 days after CCI. Subsequently, behavioral and electrophysiological assessments were performed. The M1 marker CD86 levels, M2 marker CD206 levels, and concentrations of pro-inflammatory and anti-inflammatory cytokines in the injured median nerve were assessed. L. plantarum administration effectively reduced neuropathic pain behavior and the Firmicutes to Bacteroidetes ratio after CCI. Moreover, L. plantarum treatment increased serum short-chain fatty acids (SCFAs) levels, preserved myelination of the injured median nerve, and suppressed injury-induced discharges. In CCI rats treated with L. plantarum, there was a reduction in CD86 and pro-inflammatory cytokine levels, accompanied by an increase in CD206 and the release of anti-inflammatory cytokines. Furthermore, receptors for anti-inflammatory cytokines were localized on Schwann cells, and their expression was significantly upregulated in the injured nerves of CCI rats receiving L. plantarum. In conclusion, L. plantarum shifts macrophage phenotypes from M1 to M2 by promoting the production of SCFAs and enhancing the release of anti-inflammatory cytokines. Ultimately, this process preserves nerve fiber integrity and impedes the onset of neuropathic pain.

Lonicera flos and Curcuma longa L. extracts improve growth performance, antioxidant capacity and immune response in broiler chickens.

Alternatives to antibiotics are urgently needed to maintain broiler growth and health. The present study was conducted to evaluate the effects of Lonicera flos and Curcuma longa L. extracts (LCE) as antibiotic substitutes on growth performance, antioxidant capacity and immune response in broilers. A total of 480 one-day-old female broilers (WOD168) were allocated to 3 treatments with 5 replicates of 32 birds for 35 days. The 3 treatments were: an antibiotic-free basal diet (control, CON), CON +50 mg/kg spectinomycin hydrochloride and 25 mg/kg lincomycin hydrochloride (ANT), CON +500 mg/kg LCE (LCE). During the entire experimental period, supplementation of ANT and LCE increased (p < 0.01) average daily gain (ADG) and decreased (p < 0.05) feed conversion ratio (FCR), thereby resulting in greater final body weight (BW) compared with CON. Dietary LCE supplementation increased (p < 0.05) serum (glutathione peroxidase) GSH-Px, (superoxide dismutase) SOD and total antioxidant capacity (T-AOC) activities, and decreased (p < 0.05) serum malonaldehyde (MDA) concentration at day 35 compared with CON. There was no significant difference in serum catalase (CAT) activity among treatments. Birds in LCE group had lower (p < 0.05) MDA concentration and higher SOD activity in liver than those in CON and ANT groups at day 35. Birds in LCE group had higher (p < 0.05) phagocytic index and serum antibody titers to Newcastle disease virus (NDV) than those in CON group. Lower (p < 0.05) concentrations of pro-inflammatory cytokines and higher (p < 0.05) concentrations of anti-inflammatory cytokines in serum and liver were observed in birds fed LCE diet than those fed CON diet. In conclusion, dietary supplementation of LCE improved growth performance by enhancing antioxidant capacity, strengthening immune system and alleviating inflammation, which has potential as antibiotic alternatives.

The role of cytokines and chemokines in the maintenance of chronic pain-a pilot study.

The immune system is believed to be important in the initiation and maintenance of chronic pain. The aim was to investigate whether patients with chronic painful polyneuropathy (PP) differ in cytokine profiles of serum and/or cerebrospinal fluid (CSF) compared with pain-free controls. Thirty-nine patients (16 women and 23 men, mean age, 69.2 ± 12.7 years, range 41-92 years) with PP (mean duration 43 ± 48.3 months) were phenotyped with quantitative sensory testing and electroneurography, and serum and CSF samples were analyzed by 40-multiplexed, bead-based cytokine immunoassays. Results were compared with 36 age- and gender-matched patients with normal pressure hydrocephalus and absence of abnormal CSF findings. Compared with controls, patients with PP had lower concentrations of several proinflammatory and anti-inflammatory chemokines and cytokines in CSF, and others showed the same tendency, among these were tumor necrosis factor-α (14.1 ± 10.0 vs 23.9 ± 16.4 pg/mL, P < 0.005), interleukin (IL)-2 (0.6 ± 0.4 vs 1.2 ± 0.6 pg/mL, P < 0.0001), IL-6 (4.7 ± 6.8 vs 7.3 ± 9 pg/mL, P = 0.001), and IL-10 (7.5 ± 6.8 vs 16.8 ± 19.2 pg/mL, P < 0.01), whereas no differences were observed in serum. Results suggest that (1) inflammatory mediators play a minor role in the maintenance of chronic pain in contrast to initiation of acute pain, (2) chemokines/cytokines are downregulated in chronic pain, or (3) chemokines/cytokines have a protective role for nerve regeneration that is disturbed in patients with chronic pain.

Preliminary results of anti-inflammatory cytokine concentrations predicting therapy outcome in panic disorder

BackgroundPatients with panic disorder (PD) show alterations of the immune reactivity to acute stress, which could serve as a marker for effective treatment. Nevertheless, the effect of immune reactivity under acute stress before treatment on therapy outcome remains unclear. MethodsA total of N = 16 PD patients performed the Trier Social Test. Blood sample collection of anti-inflammatory cytokine IL-10 accompanied the TSST. The Mobility Inventory was handed out for the assessment of avoidance behavior before and after treatment. Area under the curve with respect to the ground (AUCG) and increase (AUCI) were calculated for assessed cytokine levels and were used as predictors for therapy outcome in regression analyses. ResultsAUCG significantly predicts avoidance behavior in company after treatment (β = −0.007, p = .033) but not avoidance behavior alone (β = −0.003, p = .264). AUCI does not significantly predict therapy outcome. ConclusionHigher concentrations of anti-inflammatory cytokine IL-10 under acute stress before treatment predicts less avoidance behavior in company after therapy. Immune markers seem to play a crucial role in the maintenance of mental disorders such as PD. Underlying mechanisms and IL-10 as a marker for individualized treatments should be investigated in future studies.

Myocardial Remodeling Markers in Hypertensive and Overweight or Obese Patients

Pro-inflammatory and anti-inflammatory cytokines can be used as markers of the severity of the arterial hypertension (AH) and the risk of its complications. The objective: to analyze the significance of interleukin-10 (IL-10) and interleukin-1β (IL-1β) as markers of myocardial remodeling in patients with arterial hypertension (AH) and overweight or obesity. Materials and methods. 103 patients with AH (60 women and 43 men) took part in the study. The average age of the participants was 53.21±8.5 years, the average duration of AH – 8.2±6.3 years. The patients were divided into two groups according to the level of IL-10. The first group included 80 (78%) patients with AH and body mass index (BMI) ≥25 kg/m2 who had a normal level of IL-10 (up to 32 pg/ml), the second group included 23 (22%) individuals with increased anti-inflammatory cytokine. Also, the patients were divided into two groups according to cytokine levels. The first group included 74 (72%) patients with AH and overweight or obesity (the level of IL-1β was up to 11 pg/ml), the second group included 29 (28%) patients with an elevated level of IL-1β. All subjects underwent an anthropometric measurement, clinical and laboratory examination, and determination of the level of anti-inflammatory cytokine IL-10 and pro-inflammatory cytokine IL-1β by enzyme immunoassay method. Results. The results of pro-inflammatory and anti-inflammatory cytokine concentrations (IL-1β and IL-10, respectively) were different. It was found that the level of IL-10 does not depend on the age of patients and the duration of AH, but there is a direct relationship between the level of the anti-inflammatory cytokine and BMI (35.8±5.7 kg/m2 vs. 32.4±5.7 kg/m2; p&lt;0.05) with fasting glycemia level (r=0.3; p&lt;0.05). It is also indicated that patients AH and increased BMI have on average a significantly longer QT interval (0.40±0.07 s vs. 0.36±0.04 s; p&lt;0.05). It was determined that 13% of patients with elevated anti-inflammatory cytokine levels had QT prolongation. In 39% of cases, an increase in the mass index of the myocardium of the left ventricle was found (twice more among women). A direct correlation between the level of homocysteine and pro-inflammatory (r=0.31; p&lt;0.05) and anti-inflammatory cytokines (r=0.47; p&lt;0.05) was determined. At the same time, patients with elevated levels of IL-1β had a direct correlation with left ventricular myocardial mass index (r=0.42; p&lt;0.05) and average daily mean arterial pressure (r=0.85; p&lt;0.005). Conclusions. The anti-inflammatory cytokine IL-10 has greater prognostic significance than the pro-inflammatory cytokine IL-1β. An increased level of IL-10 in patients with AH and BMI ≥25 kg/m2 may indicate an adaptive reaction of the organism’s immune response. A high level of IL-10 in this cohort of patients is associated with worse control of blood pressure levels and can be considered as a predictor of the development of cardiac arrhythmias.

Ramadan-specific nutrition education improves cardio-metabolic health and inflammation-a prospective nutrition intervention study from Pakistan.

There are recent reports that Ramadan fasting (RF) results in weight gain instead of weight loss. In addition, the data on the efficacy of brief nutrition education on healthy eating practices in Ramadan for better health are scarce. Therefore, a study was conducted to investigate the effects of brief nutrition education before the start of RF on healthy eating practices during RF. For this purpose, a prospective observational study focused on "Dietary Education and Awareness for Ramadan (DEAR)" as an intervention was carried out. The participants (n = 74) were recruited and divided into two groups, i.e., intervention and control groups (n = 37 each). As an intervention, nutrition education lessons were given before and during RF month. The control group did not attend these nutrition education lessons. Data on anthropometrics, dietary intake, and other parameters were collected at three time points: before, in the end, and 4 weeks after RF. Weight was measured in kg; height, waist circumference (WC), and hip circumference (HC) were measured in cm; and body mass index (BMI) was calculated. Waist-to-hip ratio (WHR) was calculated by dividing the waist value by the hip value. Body composition analysis was performed by the body composition analyzer (BF-907). Blood pressure (BP) was measured using a validated automated blood pressure. A 3-5 ml of venous blood was collected, and plasma and serum were separated. Serum and plasma samples were processed for general blood chemistry (blood lipid profile, glucose, and CRP) within 2 h. CRP was determined by the immunoturbidimetry method using an auto-analyzer. An enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine/chemokines. Adherence to nutrition education (intervention) was assessed. The results show that nutrition education has positive effects on overall nutrition. Significant improvement in dietary adherence to dietary advice in the intervention group was noted. Significant BW loss (mean loss: 1.21 kg) in the intervention group was observed. The majority (63.3%) had lost BW ≥ 1.0 kg. Other changes observed as a result of the intervention included improvements in blood glucose, cholesterol, CRP levels, and systolic and diastolic BP. There was a notable shift in pro- and anti-inflammatory cytokine concentrations: IL-7, IL-4, and TGF-α decreased, while IL-2, TNF-α and resistin, IL-1 RA, IL-17 A, and sCD40 increased. In conclusion, RF resulted in a loss in mean BW and an improvement in related blood chemistry and cytokine profiles. Furthermore, nutrition education before RF resulted in better nutrition practices during RF and a desirable healthy BW, blood lipid, and cytokine profiles.

Аутосенсибилизация при злокачественных новообразованиях

Autoantibody formation, as a physiological mechanism of homeostatic regulation, leads to pathological processes when overexpressed. Autoantibodies are produced when the concentration of autoantigens increases, which occurs as a result of tumour necrotization and metastasizing. Autosensitization in known to develop in chronic inflammatory and tumour processes. It is of interest to clarify the significance of antiinflammatory cytokines for the formation of autoantibodies in malignant neoplasms. The purpose of this article was to identify the link between autoantibody formation and concentrations of anti-inflammatory cytokines in cancer patients. Materials and methods. Immunoassay data of 210 cancer patients of Biokor medical company (Arkhangelsk) were analysed. In the peripheral venous blood, the following were measured: antibodies against phospholipid (IgM, IgG), thyroid peroxidase (anti-TPO) and streptolysin (anti-streptolysin O), anti-double stranded DNA (anti-dsDNA) and anti-ribonucleoprotein (anti-RNP), as well as interleukins (IL) 1β, 4, 6, 10 and 13, and tumour necrosis factor (TNF-α). Results. High frequency of elevated concentrations of anti-dsDNA, antiRNP and anti-streptolysin O in the blood of cancer patients was recorded (51.72, 40.48 and 34.78 %, respectively). Most often, increased levels of anti-dsDNA were found, their mean concentrations being the highest as well. The frequency of elevated concentrations of antiphospholipid antibodies was 11.11 % for IgM and 18.42 % for IgG. Increased anti-TPO levels were observed in 14.29 % of cases. Elevated IL-10, IL-1ß and IL-4 were found in 86.90, 23.81 and 10.81 % of cased, respectively, while IL-6 and IL-13 in 5.71 and 3.85 % of cases, respectively. Mean concentrations of the cytokines under study were within the physiological limits, except for IL-10 and TNF-α, which were increased. Elevated concentrations of autoantibodies were associated with increased blood levels of TNF-α and IL-10. Thus, abnormally high blood concentrations of IL-10, which reduces cellular receptor activity, can indirectly contribute to a decrease in the activity of autoantigen disposal and clearance and prolong autosensitization.

Extracellular vesicles of iPS cells highly capable of producing HGF and TGF-β1 can attenuate Sjögren's syndrome via innate immunity regulation

Previous studies have demonstrated that extracellular vesicles (EVs) from dental pulp stem cells (DPSCs), which release abundant hepatocyte growth factor (HGF) and transforming growth factor-β1 (TGF-β1), contribute to the pathogenesis of Sjögren's syndrome (SS). However, depending on the condition of DPSCs, this effect is often not achieved. In this study, we established induced pluripotent stem (iPS) cells highly capable of releasing HGF and TGF-β1 and iPS cells barely capable of releasing them, and administered each EV to SS model mice to see if there was a difference in therapeutic effect. EVs were collected from each iPS cell and their characteristics and shapes were examined. When they were administered to SS model mice, the EVs from iPS cells with higher concentrations of HGF and TGF-β1 showed significantly reduced inflammatory cell infiltration in salivary gland tissues, increased saliva volume, and decreased anti-SS-A and anti-SS-B antibodies. A comprehensive search of microRNA arrays for differences among those EVs revealed that EVs from iPS cells with higher concentrations of HGF and TGF-β1 contained more of the let-7 family. Thereafter, we examined the expression of toll-like receptors (TLRs), which are said to be regulated by the let-7 family, by qPCR, and found decreased TLR4 expression. Focusing on MAPK, a downstream signaling pathway, we examined cytokine concentrations in mouse macrophage culture supernatants and Western blotting of murine splenic tissues and found higher concentrations of anti-inflammatory cytokines in the EVs-treated group and decreased TLR4, NF-κB and phosphorylation (p)-p-38 MAPK expression by Western blotting. Alternatively, p-Smad2/3 was upregulated in the EVs-treated group. Our findings suggest that the let-7 family in EVs may suppress the expression of TLR4 and NF-κB, which may be involved in the suppression of MAPK-mediated pro-inflammatory cytokine production.

Effect of In Ovo Administration of a Multi-Strain Probiotic and Zinc Glycine Chelate on Antioxidant Capacity and Selected Immune Parameters in Newly Hatched Chicks.

The aim of this study was to determine the effect of in ovo co-supplementation of chicken embryos with a multi-strain probiotic containing effective microorganisms and zinc glycine chelate on total antioxidant capacity; concentrations of sulfhydryl groups, bityrosine bridges, formylkynurenines, hydroperoxides, proteins, corticosterone, pro- and anti-inflammatory cytokines and heat shock proteins; and the activity of catalase and superoxide dismutase in the serum, yolk sac and tissues of broiler chickens at 12 h and at 7 days after hatching. The results indicate high SOD activity in the small and large intestines of chicks at 12 h post-hatch in the groups receiving the multi-strain probiotic and in the small intestine and yolk sac of birds receiving the multi-strain probiotic and Zn-Gly chelate. High concentrations of TNF-α and IFN-γ in the yolk sac and serum after in ovo administration of Zn-Gly chelate were observed 12 h after hatching. The use of a probiotic and a probiotic with Zn-Gly chelate increased the total antioxidant capacity in the tissues of chickens. It can be concluded that in ovo administration of a multi-strain probiotic and Zn-Gly chelate can maintain the oxidant/antioxidant balance in chickens and increase the defense capacity against oxidative stress.

L-F001, a multifunctional fasudil-lipoic acid dimer, antagonizes hypoxic-ischemic brain damage by inhibiting the TLR4/MyD88 signaling pathway.

Neonatal hypoxic-ischemic brain damage (HIBD) is a serious inflammatory injury. At present, the standard treatment for this disease is hypothermia therapy, and the effect of drug intervention is still limited. L-F001 is a compound of fasudil and lipoic acid. Previous in vitro experiments have confirmed that L-F001 has anti-inflammatory neuroprotective functions. However, its therapeutic effect on neonates with HIBD remains unknown. This study was aimed at exploring the therapeutic effect of L-F001 on HIBD rats. The newborn rats were divided into three groups: Sham operation group, HIBD group, and HIBD+L-F001 group. HE staining, Nissil staining, the immunofluorescence of iNOS and COX-2, ELISA (IL-1β, IL-6, TNF-α, and IL-10), and western blotting analyses were performed to determine the therapeutic effect of L-F001. Finally, we evaluated the growth and development of each group by measuring body weight. The hippocampal structure of HIBD rats was disordered, and the Nissil body was small and shallow. The expressions of iNOS and COX-2 in HIBD rats were increased, whereas the expressions of IL-1β, IL-6, and TNF-α in plasma were upregulated, and the expression of IL-10 was decreased. L-F001 could improve the tissue structure and reduce the expression of iNOS and COX-2 in HIBD rats. Meanwhile, L-F001 could also reduce the expression of pro-inflammatory cytokines and restore the content of anti-inflammatory cytokines in plasma. We further found that the TLR4 pathway was activated after hypoxic-ischemia in neonatal rats. L-F001 could inhibit the activation of TLR4 pathway. Finally, we found that after L-F001 treatment, the body weight of HIBD rats increased significantly compared with the untreated group. L-F001 antagonizes the inflammatory response after hypoxic-ischemia by inhibiting the activation of the TLR4 signaling pathway, thus playing a neuroprotective role. L-F001 may be a potential therapeutic agent for neonatal HIBD.

Disturbed Cytokine Profile in Adjuvant Arthritis – A Target of the Therapeutic Potential of Dendritic Cells Derived From Cryopreserved Precursors

Background. One of the primary causes of rheumatoid arthritis development is the disruption of the immune system's natural tolerance to its own antigens, leading to an imbalance in the body's cytokine profile. A promising method of correcting such a condition is restoring antigen-specific tolerance, in the formation of which tolerogenic dendritic cells (tolDCs) take part. Objective. Experimental substantiation of the possibility of correcting the cytokine profile of animals with adjuvant arthritis (AA) by using tolDCs from cryopreserved bone marrow precursors. Methods. The study was carried out on the CBA/H mice. The development of AA was assessed using a clinical indicator – the arthritis index. The levels of pro- (TNF-a, IL-6, IFN-g) and anti-inflammatory (IL-10, IL-4) cytokines in the blood serum of AA-afflicted animals were measured before and after administration of tolDCs. These tolDCs were obtained from native (NatDCs) or cryopreserved (CryoDCs) using different methods bone marrow mononuclear cells (MNCs). On the 14th day after inducing AA, the animals received intravenous injections of tolDCs (5´105/mouse). One week later, the cytokine levels in the animals' blood serum and the arthritis index were assessed. Results. Throughout the development of AA, a unidirectional increase in TNF-α and IL-6 levels and a reduction in the content of anti-inflammatory cytokines were observed, which was accompanied by joint swelling in the animals. CryoDCs exhibited a more pronounced corrective effect on both pro- and anti-inflammatory cytokines compared to NatDCs, as evidenced by a decrease in the arthritis index, a clinical manifestation of the pathology. Conclusions. The possibility of correcting the disturbed cytokine profile and the clinical state of animals during the development of AA through the use of tolDCs derived from cryopreserved MNCs has been proven. Specific cryopreservation conditions for MNCs have been developed, which facilitate the generation of tolDCs from them with a greater capacity, compared to derivatives of native MNCs, to correct the cytokine profile and clinical status of animals with AA.

Elevated Levels of Cytotoxicity, Cytokines, and Anti-SARS-CoV-2 Antibodies in Mild Cases of COVID-19.

Current evidence shows higher production of cytokines and antibodies against severe acute respiratory coronavirus 2 (SARS-CoV-2) in severe and critical cases of Coronavirus Disease 2019 (COVID-19) in comparison with patients with moderate or mild disease. A recent hypothesis proposes an important role of genotoxicity and cytotoxicity in the induction of the cytokine storm observed in some patients at later stages of the disease. Interestingly, in this study, we report significantly higher levels of interleukin (IL)-1β, IL-6, MCP-1, and IL-4 cytokines in mild COVID-19 patients versus severe cases, as well as a high frequency of karyorrhexis (median [Me] = 364 vs. 20 cells) and karyolysis (Me = 266 vs. 52 cells) in the mucosal epithelial cells of both groups of patients compared with uninfected individuals. Although we observed higher levels of anti-SARS-CoV-2 IgM and IgG antibodies in COVID-19 patients, IgM antibodies were significantly higher only in mild cases, for the N and the S viral antigens. High levels of IgG antibodies were observed in both mild and severe cases. Our results showed elevated concentrations of proinflammatory and anti-inflammatory cytokines in mild cases, which may reflect an active innate immune response and could be related to the higher IgM and IgG antibody levels found in those patients. In addition, we found that SARS-CoV-2 infection induces cytotoxic damage in the oral mucosa, highlighting the importance of studying the genotoxic and cytotoxic events induced by infection and its role in the pathophysiology of COVID-19.