TNF-α In Patients Research Articles

Oral Dysbiosis and Inflammation in Parkinson's Disease.

Background:Oral microbiota has largely escaped attention in Parkinson’s disease (PD), despite its pivotal role in maintaining oral and systemic health.Objective:The aim of our study was to examine the composition of the oral microbiota and the degree of oral inflammation in PD.Methods:Twenty PD patients were compared to 20 healthy controls. Neurological, periodontal and dental examinations were performed as well as dental scaling and gingival crevicular fluid sampling for cytokines measurement (interleukine (IL)-1β, IL-6, IL-1 receptor antagonist (RA), interferon-γ and tumor necrosis factor (TNF)-α). Two months later, oral microbiota was sampled from saliva and subgingival dental plaque. A 16S rRNA gene amplicon sequencing was used to assess bacterial communities.Results:PD patients were in the early and mid-stage phases of their disease (Hoehn & Yahr 2–2.5). Dental and periodontal parameters did not differ between groups. The levels of IL-1β and IL-1RA were significantly increased in patients compared to controls with a trend for an increased level of TNF-α in patients. Both saliva and subgingival dental plaque microbiota differed between patients and controls. Streptococcus mutans, Kingella oralis, Actinomyces AFQC_s, Veillonella AFUJ_s, Scardovia, Lactobacillaceae, Negativicutes and Firmicutes were more abundant in patients, whereas Treponema KE332528_s, Lachnospiraceae AM420052_s, and phylum SR1 were less abundant.Conclusion:Our findings show that the oral microbiome is altered in early and mid-stage PD. Although PD patients had good dental and periodontal status, local inflammation was already present in the oral cavity. The relationship between oral dysbiosis, inflammation and the pathogenesis of PD requires further study.

Study on the Relationship Between the Imaging Characteristics of Inflammatory Infection and the Expression of Serum Cytokines in Patients with Blood Tumor

To study the relationship between the CT image characteristics of inflammatory infection in patients with blood tumor and expression of serum cytokines in patients, and provide a theoretical basis for the application of CT imaging in the diagnosis of inflammation in clinical hematologic tumor patients in the future, 110 patients with inflammatory infection of blood tumor admitted to the hospital from October 30, 2017 to December 30, 2019 were selected as experimental group (EG), and 80 patients without infection in the general blood tumor department were selected as control group (CG). CT imaging was performed on both groups of patients, and two senior doctors read the imaging features and recorded the infection. At the same time, with flow cytometry, levels of IL2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α in serum were detected. Cytokines levels and CT diagnosis results were analyzed by the working characteristic curve of the subjects. Kappa was used to test the consistency of the two physicians, and Spearman correlation was used to analyze the correlation between cytokines and CT diagnosis results. The results demonstrated that IL-6 level, IL-10 level, and TNF-α level in EG were obviously higher than those in CG (P < 0.05), and there was no obvious difference in levels of IL-2, IL-4, and IFN-γ (P > 0.05). The consistency coefficient of kappa test was 0.82. In the EG, sensitivity (Se) and specificity (Spe) of IL-6, IL-10, TNF-α, and CT diagnosis were 53.5% and 76.8%, 53.5% and 80.8%, 53.5% and 72.0%, 86.7% and 72.8%, respectively. Area under curve (AUC) was 0.686, 0.747, 0.657 and 0.859. Spearman correlation analysis (SCA) indicated obvious positive correlation between CT diagnosis results and levels of serum cytokines IL-6, IL-10, and TNF-α in both groups (P < 0.05). The results showed that the levels of IL-6, IL-10 and TNF-α in patients with inflammatory infection were obviously higher than those in patients with common blood tumor. Se and AUC area of CT image diagnosis are the highest, which has a better diagnostic value in inflammatory infection of blood tumor patients. Moreover, it is obviously correlated with cytokines levels, including IL-6, IL-10, and TNF-α, in serum.

The effect of α-lipoic acid treatment on plasma asymmetric dimethylarginine, a biomarker of endothelial dysfunction in diabetic neuropathy

IntroductionDiabetic neuropathy may develop on a background of hyperglycaemia and is associated with increased oxidative stress. Elevated asymmetric dimethylarginine (ADMA) levels are linked to oxidative stress reducing the synthesis of nitric oxide (NO) by uncoupling NO synthase. Oxidative stress induces considerable changes in nerve conduction velocity in diabetic patients. There is strong evidence that α-lipoic acid (ALA) as an antioxidant may improve nerve conduction and relieve neuropathic symptoms. We aimed to investigate the relationship between endothelial dysfunction and NO synthesis in type 2 diabetic patients with peripheral neuropathy after ALA treatment.Material and methodsFifty-four type 2 diabetic patients with neuropathy were included in the study. Serum ADMA concentration, ICAM-1, VCAM-1, oxidised low-density lipoprotein (oxLDL), and TNF-α levels were determined with Enzyme-Linked Immunosorbent Assay (ELISA). Nitric oxide concentration was measured by Griess reaction. Peripheral sensory nerve function was assessed by current perception threshold (CPT) testing. Autonomic function was assessed by Ewing’s five standard cardiovascular reflex tests composite autonomic score (CAS).ResultsAsymmetric dimethylarginine levels were significantly decreased (0.62 ±0.11 vs. 0.53 ±0.11 µmol/l, p < 0.001), as well as TNF-α concentrations (1.21 ±0.42 pg/ml vs. 1.05 ±0.5 pg/ml, p < 0.05), while NO levels were significantly increased (16.78 ±11.1 vs. 21.58 ±8.84 µmol/l, p < 0.05) after six-months of 600 mg/day ALA treatment. VCAM-1, ICAM-1, and oxLDL levels did not change significantly. The CPT and CAS significantly improved after ALA treatment. The improvement of CPT values was correlated positively with the change of ADMA levels (r = 0.58, p < 0.001). The change in ADMA level was more pronounced in responder patients based on both CPT and CAS.ConclusionsOur results suggest that ALA supplementation improves endothelial function characterised by serum levels of ADMA and TNF-α in patients with diabetic neuropathy. Changes in serum ADMA levels may predict the clinical response to ALA treatment.

Association of D-dimer, inflammatory markers, cytokines abnormality, and disease severity in COVID-19 severe/critical patients in Wuhan

目的分析2019新型冠状病毒肺炎（COVID-19）重型及危重型患者D-二聚体、炎症指标、细胞因子水平与疾病严重程度的关系。方法收集华中科技大学同济医院中法新城院区山西援鄂国家医疗一队2020年2月8日至3月25日收治的41例COVID-19患者病例资料，重型28例，危重型13例，比较不同临床分型COVID-19患者的基本临床特征，入院时D-二聚体、炎症指标[WBC、ANC、降钙素原（PCT）、超敏C-反应蛋白（hsCRP）]、细胞因子（IL-2R、IL-6、IL-8、TNF-α）水平；比较有无D-二聚体异常患者的细胞因子（IL-2R、IL-6、IL-8、TNF-α）水平；并比较抗凝治疗前后患者D-二聚体、细胞因子指标（IL-2R、IL-6、IL-8、TNF-α）水平变化。结果41例患者中，男23例（56.1%），女18例（43.9%），平均年龄（55.4±11.9）岁。危重型患者平均年龄[（61.1±10.4）岁]高于重型患者[（52.8±11.7）岁]，差异有统计学意义（t=2.264，P=0.032）。危重型患者合并高血压（χ2=10.420，P=0.001）、心血管疾病（χ2=6.972，P=0.008）、脑血管疾病（χ2=6.972，P=0.008）比例高于重型患者。危重型患者出现呼吸困难、盗汗及乏力症状比例均高于重型患者，差异均有统计学意义（χ2分别为14.898、6.972、7.823，P值分别为<0.001、0.008、0.005）。危重型患者D-二聚体、WBC、ANC、PCT、hsCRP、IL-8水平均高于重型患者，差异均有统计学意义（P值均<0.05）。D-二聚体异常患者IL-2R、IL-8、TNF-α水平均较D-二聚体正常者增高，差异均有统计学意义（P值均<0.05）。8例预防性抗凝治疗患者D-二聚体、IL-2R、IL-6、IL-8抗凝治疗后比治疗前水平降低。结论COVID-19危重型患者存在更严重的凝血-免疫功能紊乱，动态监测D-二聚体、细胞因子水平有助于早期识别COVID-19危重型患者，抗凝治疗可能通过纠正凝血-免疫功能紊乱促进疾病好转。

THE VALUE OF THE MICROBIAL FLORA OF THE NASAL AND OROPHARYNGEAL MUCOSA IN THE FORMATION OF CLINICAL AND IMMUNOLOGICAL FEATURES OF INFECTIOUS MONONUCLEOSIS IN CHILDREN

Objective. The article presents the results of studies to determine the significance of the microbial flora of the nasal mucosa and oropharynx in the formation of the clinical course and immune response in children with infectious mononucleosis (IM). Materials and methods. Under the supervision were 93 children aged three to nine years, patients with mononucleosis. In 32 children (first group), Streptococcus pyogenes at concentrations of 10-5 and higher was isolated during bacteriological examination of the mucosa of the nasopharynx and oropharynx. 30 (second group) - 10-4 degrees or less. In 31 (the third group), Staphylococcus aureus, Spirochetae buccalis, E. Coli and other bacteria, except streptococcus, were sown in smears from the mucous membrane of the nasoropharynx. The immune status of patients was assessed by indicators of levels of lymphocytes CD3+, CD4+, CD8+, CD22+ and the content of interleukins 1β, 4, TNFα. Results. The acute period of the mononucleosis in children of the first group was characterized more severe symptoms of intoxication, more severe morphological changes in the tissues of the tonsils, lymph nodes, liver and spleen. Also a significant decrease in the relative amount of CD3+, CD4+, CD8+ was observed compared with the indicators of children of the second and third groups. The increase in blood CD22+ content was more significant in children of the first group. The content of pro-inflammatory IL-1β and TNF-α in patients of all groups was significantly higher than in healthy children. The IL-4 increased in children of the second and third groups. In the period of early convalescence in children of the second and third groups, the relative content of CD3+, CD4+, CD8+ cells approached the corresponding indices of the control group. This was not observed in children of the first group. CD22+ levels in all observation groups decreased by the convalescence period, but remained high compared with the control group. In children of the studied groups, by the period of reconvalescence, a decrease in the levels of IL-1β, TNF-α is noted, more significant in children of the second and third groups. At the same time, in children of the first group, the level of pro-inflammatory interleukins by the period of reconvalescence remained at high numbers. The content of IL-4 was a significant difference in the indicators of its content in comparison with the digital characteristics of healthy ones in children of the second and third groups. Conclusion. An analysis of the results of the study found that the presence of streptococcus in its high concentration on the mucosa of the nosopharynx of children with mononucleosis already contributes to the formation of cellular immunosuppression and a pronounced reaction of pro-inflammatory interleukins at the initial stage of the disease, which, in general, leads to aggravation of the clinical manifestations of the disease and, in our opinion, may be a causative factor of a possible unfavorable course of the disease.&#x0D;

Circulating levels of cytokines are increased in restless legs syndrome.

Restless legs syndrome [RLS] is known as a disease of iron and dopaminergic dysregulation but inflammatory processes might also have a role in the pathogenesis. In this study, we compared the circulating levels of hsCRP, IL-1β, IL-6, and TNF-α in patients with primary restless legs syndrome [RLS] and healthy control subjects. We prospectively included 29 patients with primary RLS and 65 healthy controls [HC], all age-sex matched. The diagnosis of RLS was established using international guidelines. IRLSSG Severity Scale was used to evaluate the severity of RLS. Plasma levels of hsCRP, IL-1β, IL-6, and TNF-α were measured in all participants. The mean age of patients was 37.8 ± 11.3 and 52% of RLS group were women. Serum IL-1β, IL-6, and TNF-α levels of the patient group were statistically significantly higher compared to HC [p < 0.001 for all variables]. Plasma levels of hsCRP did not differ between groups. There were 8 patients with mild RLS [28%], 13 patients with moderate RLS [45%], and 8 patients with severe RLS [28%]. Only IL-6 values were significantly different between the groups. In the severe group, the value of IL-6 was significantly higher than in the other groups [p: 0.03]. These results showing higher circulating levels of inflammatory cytokines in patients with RLS support the notion that inflammation may be involved in the pathogenesis of primary RLS. However, it is necessary to perform further studies to determine if this finding is a cause or an effect.

The Comparison of Tnf α (Tumor Necrosis Factor α) Serum Levels Between Cytotoxin - Associated Gene A (Caga) Positive and Negative in Patients with Gastritis Helicobacter pylori

Background: Helicobacter pylori (H. pylori) infection is the common cause of chronic gastritis in the world that is around 80% in addition to other causes such as autoimmune diseases, drugs, idiopathic and others. The pathogenesis of H. pylori associated with virulence factors consisting of cytotoxin - associated gene A (CagA) and vacuolating cytotoxin A (Vaca). In the case of gastritis occurred acute and chronic inflammatory responses and activation cytokines that cause inflammation of mucous which TNF-α levels increased in patients gatritis H. pylori. Levels of serum TNF-α was found higher in patients infected with H. pylori with CagA positive. The purpose of this study is to investigate the comparison between TNF-α serum level in H. pylori gastritis patients with Cag A (+) and CagA (-).Method: The study was conducted with a cross-sectional design in 30 patients with dyspepsia, using PADYQ score. We performed gastroscopy, biopsy, and CLO test to prove the existence of H. pylori. Furthermore, we used PCR to assess CagA (+) and CagA (-), and ELISA method to measure TNF-α serum level.Results: From 30 subjects, 18 men (60%), 12 women (40%), and the mean age was 53.5 years, the majority of the ethnic was Bataknese (53.3%), patients with H. pylori gastritis with CagA (+) were 21 (70%) and patients with H. pylori gastritis with CagA (-) were 9 (30%). We found the mean serum levels of TNF-α was higher (3.48) in H. pylori gastritis with CagA (+) than the CagA (-) (1.29) with p value was 0.001.Conclusion: We found increased serum levels of TNF-α in patients with CagA (+) compared to Cag A (-) H. pylori gastritis.

Relationship of Serum Levels of IL-17, IL-18, TNF-α, and Lung Function Parameters in Patients with COPD, Asthma-COPD Overlap, and Bronchial Asthma.

Determination of markers of systemic inflammation is one of the important directions in the study of pathogenesis and improvement of diagnosis of chronic obstructive pulmonary disease (COPD), asthma-COPD overlap (ACO), and bronchial asthma (BA). The aim of our work was a comparative study of the features of changes in serum levels of IL-17, IL-18, and TNF-α in patients with COPD, ACO, and BA with various severity of the disease, as well as evaluation of the relationship between the level of these cytokines and lung ventilation function. A total of 147 patients with COPD (n = 58), ACO (n = 57), and BA (n = 32) during a stable period have been examined in this study. The control group included 21 healthy nonsmokers with similar sex-age indicators. Serum levels of IL-17, IL-18, and TNF-α were determined by ELISA. The concentrations of these cytokines in the circulation in the studied patients with COPD, ACO, and BA were higher than those in healthy nonsmokers (p ≤ 0.001). IL-17 and IL-18 levels in the blood serum were comparable in all examined patients. The mean TNF-α concentrations in the circulation in COPD and ACO were significantly higher than those in BA (p < 0.001). In patients with COPD, the levels of IL-17 and TNF-α increased progressively against the background of a decrease in numerous spirometric indicators, which allows us to consider these cytokines as systemic biomarkers of disease severity. In BA, the inverse correlations between the level of IL-17 and FEV1/FVC (%) and FEV1 have been found. In patients with ACO, the increase in IL-18 levels was associated with a decrease in FEV1 and TNF-α with FEV1/FVC (%). These findings indicate that IL-17, IL-18, and TNF-α can participate in the mechanisms of systemic inflammation and the genesis of disorders of airway obstruction in COPD, AСO, and BA. An increase in the levels of IL-17 and TNF-α may be associated with impaired bronchial patency in COPD and BA. The established associations of the IL-18 concentration in the blood serum and FEV1 only in patients with ACO allow using the level of IL-18 as a potential marker of the degree of impaired airway obstruction in this disease.

Expression of ADP and TNF-α in patients with gestational diabetes mellitus and its relationship with pregnancy outcomes.

Expression of adiponectin (ADP) and tumor necrosis factor-α (TNF-α) in patients with gestational diabetes mellitus and its relationship with pregnancy outcomes was explored. A total of 78 patients with gestational diabetes mellitus admitted to Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University from June 2017 to December 2018 were enrolled as an experimental group, and further 70 healthy pregnant women in physical examination during the same period were enrolled as a control group. Concentrations of ADP and TNF-α were determined and compared between the two groups. The patients were divided into high ADP expression group (≥6.84), low ADP expression group (<6.84), high TNF-α expression group (≥6.17) and low TNF-α expression group (<6.17). Corresponding two groups were compared in terms of adverse pregnancy outcomes, respectively, and they were also compared with the control group. The clinical association between ADP and TNF-α was analyzed. TNF-α was highly expressed in the blood of patients with gestational diabetes mellitus, while ADP expression was low in the blood. The low expression of ADP was related to age, pregestational body mass index (BMI), gestational week, medical history and family history of diabetes mellitus (all P<0.05), and the high expression of TNF-α was related to age, pregestational BMI, gestational week, medical history, amniotic fluid volume, abortion history, and family history of diabetes mellitus (all P<0.05). The experimental group faced a higher risk of adverse pregnancy outcomes than the control group. Both ADP and TNF-α are abnormally expressed in the patients with gestational diabetes mellitus, and TNF-α is affected by more of the factors. The concentrations of ADP and TNF-α affect the pregnancy outcomes. It suggests that ADP and TNF-α can be used as indexes for predicating pregnancy outcomes, and for judging the disease conditions and treatment of patients.

An independent component analysis reveals brain structural networks related to TNF-\u03b1 in drug-na\xefve, first-episode major depressive disorder: a source-based morphometric study

In a previous mouse study, social defeat stress-induced microglial activation released tumor necrosis factor-α (TNF-α), leading to neuronal changes in the prefrontal cortex (PFC) and behavioral changes (anxiety). We aimed to investigate the relationship between gray-matter (GM) structural networks and serum TNF-α in patients with major depression disorder (MDD) using multivariate source-based morphometry (SBM). Forty-five first-episode and drug-naïve MDD patients and 38 healthy subjects (HSs) were recruited. High-resolution T1-weighted imaging was performed and serum TNF-α levels were measured in all MDD patients and HSs. After acquiring GM structural networks using SBM, we compared the Z-transformed loading coefficients (Z-scores) between MDD patients and HSs, and investigated the relationship between the Z-scores and the serum TNF-α levels in MDD patients. The serum TNF-α levels in MDD patients were significantly higher than those in HSs. We extracted two independent GM structural networks (the prefrontal network and the insula-temporal network) with significant differences between MDD patients and HSs (−0.305 ± 0.85 and 0.253 ± 0.82; P = 0.03 in the prefrontal network, and −0.268 ± 0.86 and 0.467 ± 0.71; P < 0.01 in the insula-temporal network). The serum TNF-α levels were significantly correlated with the Z-scores in the prefrontal network after Bonferroni correction (r = −0.419, p < 0.01); however, the correlation in the insula-temporal network was not significant (r = −0.290, p = 0.11). Elevated serum TNF-α levels in the early stage of MDD were associated with alteration of the prefrontal network.

The utility of serum C-C chemokine ligand 1 in sarcoidosis: A comparison to IgG4-related disease

We previously reported higher levels of C-C chemokine ligand (CCL) 1 in the bronchoalveolar lavage (BAL) fluid (BALF) of patients with sarcoidosis than in BALF of patients with immunoglobulin G4 (IgG4)-related disease (IgG4-RD), indicating that CCL1 might act as a marker of disease activity in sarcoidosis. Notably, less invasive sampling sources are desirable, as BAL cannot always be performed due to its inherent risk. In this study, we sought to decipher the correlation between serum levels of CCL1 and clinical characteristics of sarcoidosis. Serum samples were obtained from 44 patients with clinically confirmed sarcoidosis, 14 patients with IgG4-RD, and 14 healthy controls. The clinical and radiological findings were retrospectively evaluated. Serum levels of CCL1 were measured using a sandwich enzyme-linked immunosorbent assay. Serum levels of other 17 cytokines and chemokines were measured using a MILLIPLEX® MAP KIT and Luminex® magnetic beads. Serum levels of CCL1 were significantly higher in patients with sarcoidosis than in patients with IgG4-RD and healthy controls. Serum CCL1 was positively correlated with the degree of hilar lymph node swelling on chest computed tomography and serum levels of soluble interleukin 2 receptor. Positive correlations were also observed between serum CCL1 and total cell counts, lymphocyte counts in BALF, and serum T helper 1 mediators such as IP-10 and TNF-α in patients with sarcoidosis. Serum CCL1 levels were significantly elevated in sarcoidosis and correlated with clinical parameters of the disease. In addition, serum and BALF levels of CCL1 were positively correlated in a statistically significant manner. Although further research in this field is necessary, CCL1 might have the potential to be a reliable serological marker of disease activity in sarcoidosis.

The relationship between urinary and plasma levels of tumor necrosis factor alpha and various stages of chronic kidney disease in patients with type II diabetes mellitus

Introduction: The concept of diabetic nephropathy, as a metabolic disease, is now being replaced by chronic low-grade inflammatory disease. Tumor necrosis factor alpha (TNF-α) is a proinflammatory cytokine that plays an important role in the pathogenesis and clinical outcomes of diabetic nephropathy. Objectives: This study aimed to determine the relationship between plasma and urinary levels of TNF-α and chronic kidney disease (CKD) in patients with type 2 diabetes mellitus. Patients and Methods: In this descriptive-analytical study, patients with type 2 diabetes mellitus who referred to the endocrine clinic in Kashan (2016) were enrolled in the study and their clinical and laboratory data were recorded. Albumin/creatinine ratio (ACR) and glomerular filtration rate (GFR) were calculated. The patients were divided into three groups based on their GFR. Serum and urinary levels of TNF-α were determined by ELISA and were compared between the studied groups. Results: A total of 128 patients were evaluated. Of all, 35 patients (27.3%), 39 patients (30.4%), and 54 patients (42.3%), respectively, were suffering from stage 1, stage 2, and stage 3 CKD. The plasma levels of TNF-α in patients with stage 1, 2, and 3 CKD, were 66.20 ± 33.27 pg/mL, 67.47 ± 42.98 pg/mL, and 77.32 ± 47.23 pg/mL respectively, since the difference among them was not significant (P= 0.417). In addition, the urinary levels of TNF-α in patients with stage 1, 2, and 3 CKD, respectively, were 88.18 ± 26.66 pg/mL, 97.41 ± 57.76 pg/mL, and 101.18 ± 60.47 pg/mL, since no significant difference was observed between the three groups (P=0.957). Conclusion: Based on the results of this study, with changing the stage of CKD, the serum and urinary levels of the TNF-α increases too, although this increase is not significant. Moreover, the plasma and urinary levels of the TNF-α have a direct and significant relationship with each other. It is recommended to conduct further studies in this field.

Evidence of Systemic Responses to Viral Pathogens using Malondialdehyde, Tumor Necrosis Factor Alpha and Superoxide Dismutase

Background and Aim: Infectious agents are triggers of oxidative stress and inflammation. This work was designed to determine evidence of systemic responses to viral pathogens using malondialdehyde, tumor necrosis factor alpha and superoxide dismutase. Methods: The subjects recruited for this study include 23 HCV mono-infected volunteers (aged 24-67 years; Male-10; Female-13), 30 HBV mono-infected volunteers (aged 24-67 years; Male-15; Female-15), 18 HIV mono-infected volunteers (aged 24-67 years; Male-8; Female-10), 23 Viral (HCV, HIV, HBV) Co-infected volunteers (aged 24-67 years; Male-10; Female-13) and 50 age matched control volunteers who were not infected with HCV, HIV or HBV (Female-25; Male-25). Subjects tested negative to Acid Fast Bacilli (AFB) and Plasmodium tests were recruited. Test subjects who have not initiated antiviral therapy were recruited for the study. Five milliliters of venous blood was obtained from each of the subjects into lithium heparinized bottles for the assay of HCV, HIV, HBV, TNFα by ELISA, SOD, MDA by Colorimetry, Giemsa thick blood film staining for plasmodium while sputum samples were obtained from each of the subjects for Ziehl Neelsen staining for Acid Fast Bacilli(AFB). Results: There was a significant increase in plasma MDA and TNF α in patients with viral co-infection compared with control and patients with mono-infections of HCV, HBV and HIV (p<0.05). There was a significant decrease in plasma SOD in patients with viral co-infection compared with control and patients with mono-infection of HBV (p<0.05; Table 1, 2; Figure 1, 2). The result also showed a significantly lower plasma SOD in patients with viral co-infection, mono-infection of HIV, HCV and HBV than the results obtained in the control subjects (p<0.05). There was a significant increase in plasma TNF-α in patients with viral co-infection compared with control and patients with mono-infections of HCV, HIV and HBV (p<0.05). The result also showed a significantly higher plasma TNF-α in patients with viral co-infection, mono-infection of HIV, HCV and HBV than the results obtained in the control subjects (p<0.05). Conclusion: The work revealed a significant evidence of systemic responses to viral pathogens as indicated by increased plasma malondialdehyde, tumor necrosis factor-alpha, and decreased plasma superoxide dismutase in viral mono and coinfections.

Salivary Cytokines and Airways Disease Severity in Patients with Cystic Fibrosis.

About 50% of patients with cystic fibrosis (CF) have sinonasal complications, which include inferior turbinate hypertrophy (NTH) and/or nasal polyposis (NP), and different degrees of lung disease, which represents the main cause of mortality. Monitoring of sinonasal disease requires complex instrumental procedures, while monitoring of lung inflammation requires invasive collection of bronchoalveolar lavage fluid. The aim of this study was to investigate the associations between salivary cytokines levels and CF-related airway diseases. Salivary biochemical parameters and cytokines, i.e., interleukin-6 (IL-6), IL-8, and tumor necrosis factor alpha (TNF-α), were analyzed in resting saliva from healthy subjects and patients with CF. Patients with CF showed significantly higher levels of salivary chloride, IL-6, IL-8, and TNF-α and lower calcium levels than healthy subjects. Among patients with CF, IL-6 and IL-8 were significantly higher in patients with NTH, while TNF-α was significantly lower in patients with NP. A decreasing trend of TNF-α in patients with severe lung disease was also observed. On the other hand, we did not find significant correlation between cytokine levels and Pseudomonas aeruginosa or Stenotrophomonas maltophilia colonization. These preliminary results suggest that salivary IL-6 and IL-8 levels increase during the acute phase of sinonasal disease (i.e., NTH), while the end stages of pulmonary disease and sinonasal disease (i.e., NP) show decreased TNF-α levels.

Dynamics of background levels of serum cytokines in children with atopic dermatitis with concomitant pathology of oral mucosa in the course of optimized complex therapy

Dynamics of background levels of serum cytokines in children with atopic dermatitis with concomitant pathology of oral mucosa in the course of optimized complex therapy

Evaluation of Proinflammatory, NF-kappaB Dependent Cytokines: IL-1α, IL-6, IL-8, and TNF-α in Tissue Specimens and Saliva of Patients with Oral Squamous Cell Carcinoma and Oral Potentially Malignant Disorders.

Background: Oral squamous cell carcinoma (OSCC) is a life-threatening disease. It could be preceded by oral potentially malignant disorders (OPMDs). It was confirmed that chronic inflammation can promote carcinogenesis. Cytokines play a crucial role in this process. The aim of the study was to evaluate interleukin-1alpha (IL-1α), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNF-α) in tissue specimens and saliva of patients with OSCC and OPMDs. Methods: Cytokines were evaluated in 60 tissue specimens of pathological lesions (OSCCs or OPMDs) and in 7 controls (normal oral mucosa, NOM) by immunohistochemistry and in saliva of 45 patients with OSCC or OPMDs and 9 controls (healthy volunteers) by enzyme-linked immunosorbent assays. Results: Immunohistochemical analysis revealed significantly higher expression of IL-8 in OSCC specimens and TNF-α in OSCCs and OPMDs with dysplasia as compared to NOM. Moreover, expression of TNF-α was significantly higher in oral leukoplakia and oral lichen planus without dysplasia, whereas expression of IL-8 only in oral leukoplakia without dysplasia in comparison with NOM. Salivary concentrations of all evaluated cytokines were significantly higher in patients with OSCC than in controls. Moreover, levels of IL-8 were significantly higher in saliva of patients with OPMDs with dysplasia as compared to controls and in OSCC patients as compared to patients with dysplastic lesions. There was also significant increase in salivary concentrations of IL-6, IL-8 and TNF-α in patients with OSCC as compared to patients with OPMDs without dysplasia. Conclusion: The study confirmed that proinflammatory, NF-kappaB dependent cytokines are involved in pathogenesis of OPMDs and OSCC. The most important biomarker of malignant transformation process within oral mucosa among all assessed cytokines seems to be IL-8. Further studies on a larger sample size are needed to corroborate these results.

SUN-379 ASSOCIATION BETWEEN USE OF BIOLOGIC THERAPY FOR NON-NEPHROLOGICAL DISEASE AND ONSET OF NEPHROTIC SYNDROME IN A LARGE TERTIARY UK RENAL UNIT COHORT

The use of tumour necrosis factor-α (TNF-α) inhibitors in the management of refractory autoimmune inflammatory conditions including Rheumatoid Arthritis and Inflammatory Bowel Disease (IBD) has become increasingly prevalent overtime. TNF-α promotes inflammation through variable mechanisms, including cytokine and chemokine expression with suppression of regulatory T cells. The main factor limiting use is the serious adverse side-effect profile of these agents including infection, cardiac failure, haematological malignancies and neurological disease. Isolated case reports suggest a link between biologics and the Nephrotic Syndrome (NS). We examine a large local cohort to determine the incidence of new onset NS following use of biologic therapy. This retrospective observational study collected data from 2 large UK centres, including a tertiary renal unit with catchment population of 2.2 million. Records and histopathology reports were available from February 1995 to March 2019 at centre 1, centre 2 from November 2012 to September 2018. Clinical notes and laboratory data including histopathology were reviewed across 3 specialities (aside from nephrology) at both centres more frequently using biologics in disease management; Dermatology, Rheumatology and Gastroenterology. We noted use of any biologic therapy for patients within these specialities during this time period in each respective centre and whether patients subsequently developed clinical and histological evidence of NS, cross-referencing to renal data across both sites. 685 patients reviewed across both centres; 392 patients identified in centre 1, 20 (5%), received biologic therapy at some stage and more specifically 9 of these received TNF-α inhibition. 293 patients identified as having biopsy-proven NS at centre 2, 10 (3%) received biologic therapy and specifically 2 had received a TNF-α inhibitor during the time periods stated. Overall, 3 patients developed NS directly following targeted TNF-α therapy, 2 were female, median age of 30 (range 21-67). 1 patient received TNF-α inhibition and developed NS however biopsy was consistent with diabetic nephropathy in a long-standing diabetic and so was excluded in the final outcomes. All 3 patients had IBD. 1 patient received both Infliximab and Adalimumab, 1 received Infliximab and Vedolizumab and 1 patient Infliximab alone. Histopathology revealed 1 case of Membranous Glomerulonephropathy, 1 Minimal Change Disease (MCD) and 1 MCD / IgA nephropathy crossover. We believe this to be the largest case series to date of patients developing NS following use of biologic therapy. Interestingly, all 3 cases related to biologics targeting TNF-α in patients with pre-existing IBD. This large cohort analysis suggests overall incidence of NS following biologics is very small, however the subset identified displayed common features; patients with IBD receiving treatment with infliximab or adalimumab. From our data, causality cannot be attributed and more mechanistic work is required to determine whether this represents coincidence or a rarer adverse effect. Despite this, as biologic use becomes more widespread, it is prudent for healthcare professionals monitoring patients on biologic agents to be aware of potential nephrological adverse outcomes with these agents, adopting prospective monitoring practices such as routine urinalysis accordingly.

A Randomized Control Trial Study to Determine the Effect of Melatonin on Serum Levels of IL-1β and TNF-α in Patients with Multiple Sclerosis.

Multiple sclerosis (MS) is the most common neurological disease that happens at a young age. MS is an inflammatory disease; associated with the demyelination of the central nervous system. Therefore, some inflammatory factors are effective in the mechanism and progression of the disease. Melatonin, as a multi-effect substance including anti-inflammatory effects, can reduce symptoms of MS in patients with a change in their inflammatory factors level. In this study, 50 MS patients who were referred to the MS Society of Markazi Province were randomly selected. All patients were treated with routine MS treatment (interferon) and were divided into control (25 placebo recipients) and treatment (25 recipients of 3 mg melatonin per day for 24 weeks) groups. Anthropometric data of patients including height, weight, and age were determined. Blood samples were collected after fasting in order to determine serum levels of interleukin 1 beta (IL-1β) and tumor necrosis factor-alpha(TNF-α). Then, samples were immediately centrifuged for serum separation and sera were transferred to a freezer at -80°C and serum levels of these factors were determined; using ELISA kit. The results of this study showed that there was no significant difference between the control and treatment groups in terms of serum levels of TNF-α. However, the level of IL-1β was significantly reduced in the treatment group compared to the control group, indicating that melatonin decreases this inflammatory substance. Our findings suggest a valuable strategy in the treatment of patients who suffer from MS.

РОЛЬ МОНОЦИТОВ В ПАТОГЕНЕЗЕ РАСПРОСТРАНЁННОГО ПЕРИТОНИТА

Objective: To study the sepsis markers informativeness to assess the role of monocytes in the pathogenesis of generalized peritonitis (GP). Methods: The study included 160 patients with GP, who were divided into 3 groups, according to the stages of the disease. To establish the activity of monocytes was made a determination of the level of cytokine TNF-α and presepsin in the blood. Results: Studies showed that the level of TNF-α in patient with septic shock was reliably lower (24.5±13.3 pg/ml) than in patients with endogenous intoxication and abdominal sepsis. The value of TNF-α in deceased patients also was low – 4.8±0.9 pg/ml. This indicates a decrease in the ability of monocytes in GP at the stage of septic shock to exude a sufficient amount of pro-inflammatory cytokines in response to endotoxin aggression. The level of presepsin increased by stages and amounted to 355.6±8.6, 783.4±24.0 and 1587.7±70.5 pg/ml, respectively. This indicates the circulation in the blood of the CD14 receptor, which is able to express on monocytes, converting them into endothelial progenitor cells. Conclusions: Monocytes as endothelial progenitor cells contribute to the regeneration and restoration of endothelial function in its dysfunction that develops in GP and abdominal sepsis. In consequence of developing immunosuppression and suppression of monocyte function in the stage of septic shock, the process of renewal of endothelial cells is weakened, the secretion of pro-inflammatory cytokines, in particular TNF-α, decreases, which can contribute to an increase in mortality in septic shock. Keywords: Monocytes, abdominal sepsis, septic shock, endothelial dysfunction, progenitor cells.

Helicobacter pylori Infection and Autoimmune Thyroid Diseases: The Role of Virulent Strains.

Aim: To verify a possible association between overall H. pylori and CagA+ H. pylori infection and autoimmune thyroid diseases (AITDs). Methods: Consecutive patients with AITDs admitted to one single centre of Endocrinology during one solar year were examined. The diagnoses were Hashimoto thyroiditis (HT) in 76, Graves’ Disease (GD) in 39, and aspecific thyroiditis (AT) in 44 patients. Controls were 136 individuals without AITDs. Median values of fT3, fT4, anti-thyreoglobulin (Tg) antibodies, IL-1β, IL-6, and TNF-α in patients were compared with those in controls. H. pylori infection and CagA status were determined serologically. Structural homology of some thyroid proteins with H. pylori antigens was investigated. Results: H. pylori infection prevalence was significantly increased in GD (66.6%) and HT (64.4%) patients, vs. 29.4% of controls and 34.0% of AT. CagA seropositivity was significantly more frequent in GD (46.1%) and HT (46.9%) infected patients, vs. infected controls (20%). fT3 and fT4 median values were significantly decreased in infected CagA+ GD patients vs. uninfected GD patients. IL-1β median values were increased in patients respect to controls, independently of the clinical form of AITD. Median values of IL-6, TNF-α and anti-Tg autoantibodies in CagA infected patients were significantly higher than those measured in infected CagA− and uninfected patients and in infected CagA+ controls. The examined thyroid proteins shared putative conserved domains with numerous bacterial antigens. Conclusions: Overall H. pylori and CagA+ H. pylori infection were associated with GD and HT, putatively through an increased inflammatory status and molecular mimicry.