Serum Levels Of IL-6 Research Articles

The effect of inflammatory cytokines on occurrence of retained placenta in cattle

Background: In simple terms, retained placenta is a common issue after parturition in cattle that can affect their reproductive ability. In pregnancies with fetal growth restriction (FGR), the placenta has low anti-inflammatory cytokines and high pro-inflammatory cytokines. By looking at variations in cytokine levels in the blood, we can diagnose the condition. The focus of a recent study was to examine the role of some interleukins (Interleukins -10, Interleukins -6, Interleukins -1β), C-reactive protein (CRP) and Tumor Necrosis Factor (TNF)-α, in retained placenta occurrence in cattle.Methods: The study involved 40 cows, aged 3-8 years in the Salah-Din province. Each animal suffered from retained placenta also eleven healthy cows served as the control group in a period of January to August 2022. The blood serum was analyzed using enzyme immunoassay techniques (ELIZA) to measure the levels of IL-10, IL-6, IL-1β, CRP and TNF-α.Results: Serum levels of IL-10, IL-6, IL-1β, CRP and TNF-α showed a significant increase in cows experiencing retained fetal membranes compared to healthy cows (2.31±0.11 vs 1.41 ±0.07) (10.48±0.24 vs 5.40±0.19), (13.6±2.1 vs 4±0.9), (0.9±0.02 vs 0.32±0.04) and (60.1 ± 12.79 vs 29.5 ± 16.58) respectively.Conclusion: from the present study we conclude that IL10, IL6, IL1β and TNFα play an essential component in retained placenta incidence, and the estimation levels of these parameters in serum may be considered good indicator for occurrence in cattle. RT-PCR revealed increased expression of SDHA genes in the maternal compartment of the placenta.Keywords: Retained placenta; Cytokines; C-reactive protein

Correlation of Inflammatory Biomarkers (Interleukin-6, Interleukin-8, and Tumor Necrosis Factor-alpha) with Severity of Acute Pancreatitis

Abstract Background: Early assessment of severity of acute pancreatitis is very essential for the selection of patients who will require intensive care to prevent local complications and organ dysfunction. Several scoring systems have been developed, but these require large number of clinical and biochemical parameters, making them overly complicated and cumbersome. There is a need to develop simple clinical investigations which would help in assessing the severity of acute pancreatitis. Hence, the present study is undertaken to evaluate the role of inflammatory biomarkers (interleukin-6 [IL-6], IL-8, and tumor necrosis factor-alpha [TNF-α]) in the assessment of severity in acute pancreatitis. Materials and Methods: This cross-sectional study was conducted at a tertiary care teaching hospital in North India and enrolled 50 patients with acute pancreatitis. Serum levels of IL-6, IL-8, and TNF-α were measured within 24 h of admission. Results: The levels of IL-6, IL-8, and TNF-α were found to be significantly higher in patients with severe pancreatitis as compared to mild disease. With a cutoff level of >46.379 pg/ml, IL-6 had a sensitivity of 96.15%, specificity of 95.83%, and diagnostic accuracy of 96% for predicting progression to severe acute pancreatitis. Similarly, IL-8 >39.54 pg/mL had a sensitivity of 92.31%, specificity of 91.67%, and diagnostic accuracy of 92%. TNF-α >11.80 pg/mL had a sensitivity of 53.85%, specificity of 95.83%, and diagnostic accuracy of 74%. Conclusion: The current study results suggests that IL-6 and IL-8 levels measured within 24 h of admission can be used for predicting progression to severe acute pancreatitis.

Association of Baseline Serum Soluble Tumour Necrosis Factor Receptor Levels with the Response of Rheumatoid Arthritis to Janus Kinase Inhibitor Therapy.

The aim of this study was to investigate whether cytokines associated with tumour necrosis factor- (TNF-) α and interleukin- (IL-) 6 signalling could predict rheumatoid arthritis (RA) clinical remission (CR) with Janus kinase inhibitor (JAKinib) treatment using the Simplified Disease Activity Index (SDAI). Eighty-nine patients with RA treated with JAKinibs were enrolled, and their clinical data were collected retrospectively. CR was defined as an SDAI ≤ 3.3 after 6 months of treatment with JAKinib. The serum samples of 89 patients were analysed for IL-6, soluble IL-6 receptor (sIL-6R), soluble gp130 (spg130), and soluble TNF receptor- (sTNFR-) I and sTNFR-II titres. There were no significant differences in the baseline clinical parameters between the CR and non-CR groups. Serum levels of IL-6, sIL-6R, and sgp130 were not significantly different; whereas, the serum sTNFR-I and sTNFR-II levels were significantly lower in the CR group. Univariate and multivariate logistic regression analysis showed that the baseline log sTNFR II values (OR: 0.002; p = 0.034) were predictors of CR. Patients with RA can be stratified prior to JAKinib administration using serum sTNFR-I and sTNFR-II levels but not serum IL-6 axis cytokine levels (IL-6, sIL-6R, and sgp130).

Electrical stimulation of the dorsal motor nucleus of the vagus in male mice can regulate inflammation without affecting the heart rate

BackgroundThe vagus nerve plays an important role in neuroimmune interactions and in the regulation of inflammation. A major source of efferent vagus nerve fibers that contribute to the regulation of inflammation is the brainstem dorsal motor nucleus of the vagus (DMN), as recently shown using optogenetics. In contrast to optogenetics, electrical neuromodulation has broad therapeutic implications. However, the anti-inflammatory effectiveness of electrical stimulation of the DMN (eDMNS) and the possible heart rate (HR) alterations associated with this approach have not been investigated. Here, we examined the effects of eDMNS on HR and cytokine levels in mice administered with lipopolysaccharide (LPS, endotoxin) and in mice subjected to cecal ligation and puncture (CLP) sepsis. MethodsAnesthetized male 8–10-week-old C57BL/6 mice on a stereotaxic frame were subjected to eDMNS using a concentric bipolar electrode inserted into the left or right DMN or sham stimulation. eDMNS (500, 250 or 50 μA at 30 Hz, for 1 min) was performed and HR recorded. In endotoxemia experiments, sham or eDMNS utilizing 250 μA or 50 μA was performed for 5 mins and was followed by LPS (0.5 mg/kg) i.p. administration. eDMNS was also applied in mice with cervical unilateral vagotomy or sham operation. In CLP experiments sham or left eDMNS was performed immediately post CLP. Cytokines and corticosterone were analyzed 90 mins after LPS administration or 24 h after CLP. CLP survival was monitored for 14 days. ResultsEither left or right eDMNS at 500 μA and 250 μA decreased HR, compared with baseline pre-stimulation. This effect was not observed at 50 μA. Left side eDMNS at 50 μA, compared with sham stimulation, significantly decreased serum and splenic levels of the pro-inflammatory cytokine TNF and increased serum levels of the anti-inflammatory cytokine IL-10 during endotoxemia. The anti-inflammatory effect of eDMNS was abrogated in mice with unilateral vagotomy and was not associated with serum corticosterone alterations. Right side eDMNS in endotoxemic mice suppressed serum TNF and increased serum IL-10 levels but had no effects on splenic cytokines. In mice with CLP, left side eDMNS suppressed serum IL-6, as well as splenic IL-6 and increased splenic IL-10 and significantly improved the survival rate of CLP mice. ConclusionsFor the first time we show that a regimen of eDMNS which does not cause bradycardia alleviates LPS-induced inflammation. These eDMNS anti-inflammatory effects require an intact vagus nerve and are not associated with corticosteroid alterations. eDMNS also decreases inflammation and improves survival in a model of polymicrobial sepsis. These findings are of interest for further studies exploring bioelectronic anti-inflammatory approaches targeting the brainstem DMN.

IL-10 and IL-1β Serum Levels, Genetic Variants, and Metabolic Syndrome: Insights into Older Adults' Clinical Characteristics.

Populational aging is marked by chronic noncommunicable diseases, such as metabolic syndrome (MetS). IL-10 and IL-1β are pleiotropic cytokines with multiple biological effects linked to metabolic disorders. This cross-sectional study assessed 193 participants' IL-10 and IL-1β serum levels regarding their role in developing MetS, clinical characteristics, and their IL1B rs1143627 and IL10 rs1800890 variants' genotype frequencies in a population over 60. IL-10 levels correlated weakly with HDL levels and fat mass and inversely with triglycerides, glucose, glycated hemoglobin, and estimated average blood glucose levels. IL-10 levels were also indirectly influenced by the patient's T2DM duration, lean mass amount, and bone mineral content. Participants with altered HDL, elevated serum glucose, raised HbA1c levels, or those over 80 had reduced serum IL-10 levels compared to those with normal levels or other age groups, respectively. Women also had higher serum IL-10 levels than men. Dissimilarly, IL-1β levels correlated directly only with the number of total leukocytes and segmented neutrophils, showing only significant variations with self-reported alcohol consumption. Our study also found that those with the IL10 AA genotype (lower IL-10 levels) had a significantly higher risk of developing MetS. These findings may help direct future research and more targeted therapeutic approaches in older adults.

HERV-W upregulation expression in bipolar disorder and schizophrenia: unraveling potential links to systemic immune/inflammation status

BackgroundBipolar disorder (BD) and schizophrenia (SZ) are the two main mental disorders with unknown etiology that significantly impact individuals’ quality of life. The potential pro-inflammatory role in their pathogenesis is postulated and Human Endogenous Retrovirus W (HERV-W) is an emerging candidate to modulate this pathogenic finding. HERVs, ancient retroviruses in the human genome, may play roles in inflammation and disease pathogenesis. Despite HERVs’ involvement in autoimmune diseases, their influence on mental disorders remains underexplored. Therefore, the aim of this study was to assess the level of HERV-W-env expression and the systemic inflammatory profile through the concentration of IL-2, IL-4, IL-6, IL-10, TNF-α and INF-γ cytokines in BD and SZ patients.ResultsAll participants showed HERV-W-env expression, but its expression was higher in mental disorder patients (p < 0.01) than in control. When separated, SZ individuals exhibited higher HERV-W expression than the control group (p < 0.01). Higher serum levels of TNF-α and IL-10 were found in BD (p = 0.0001 and p = 0.001, respectively) and SZ (p = 0.01) and p = 0.01, respectively) than in the control group, while SZ showed decreased levels IFN-γ and IL-2 as compared to controls (p = 0.05) and BD patients (p = 0.05), respectively. Higher TNF-α/IL-4 and TNF-α/IL-10 ratios, and lower IFN-γ/IL-10 were observed in BD and SZ patients than controls. Significant negative correlation between HERV-W-env expression and IL-10 (r=-0.47 p < 0.05), as well as positive correlations between HERV-W-env expression and TNF-α/IL-10 or IFN-γ/IL-10 ratios (r = 0.48 p < 0.05 and r = 0.46 p < 0.05, respectively) were found in BD patients.ConclusionThese findings suggest not only a potential link between HERV-W-env expression both in BD and SZ, but also a possible involvement of systemic inflammatory status in BD patients.

Correlation between Human Boca virus and IL-23in some Iraqi patients with ischemic heart disease

Heart diseases in the Iraqi population are a significant public health concern. Iraq has experienced in the prevalence of heart diseases, including coronary artery disease, heart failure and hypertension. Different researches have shown that human Boca virus (HBoV) may be a risk factor, for some cardiac disorders. Hence, goals of resent work is to investigate roles of human Boca virus in ischemia heart disease (IHD) and to investigate roles of serum level of IL-23 in these diseases. 40 heart diseases patients and 40 controls were included. Controls were females (n=30) followed by males (n=10), while patients with IHD were 27 males and 13 females. There were highly significant variations in ages of patients and controls with (p≤0.01). The mean ± SE of age of patients with IHD was 37.90 ±0.75 years, while the mean ± SE of controls was 40.52 ±0.79 years. Lipid profile was measured. There were significant variations between patients' and controls. Also, mean ± SE of HDL was statistically significant between ischemia and control groups (85.28 ±4.31 and 55.10 ±1.23 mg/dl) with p≤0.01, respectively. The serum levels of IgG and IgM were assessed using ELISA. There was no significant variation in mean ± SE of serum level of IgM between ischemia and healthy controls (0.251 ±0.04 and. 0.341 ±0.07 ug/Ml). respectively. There were significant variations in mean ± SE of serum level of IgG between ischemia and controls (0.723 ±0.16 and. 0.076 ±0.004 ug/ml). There were highly significantly differences in Mean ± SE of serum level of 1L-23 between IHD heart diseases (0.407 ±0.073 Pg/mL) and healthy controls (0.0121 ±0.003 pg/mL) with p&lt;0.001, respectively.

A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study

Background and objective A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects. Methods Male and female subjects (n = 135; age: 25–60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured. Results CL18100F4 supplementation significantly (p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved (p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly (p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants’ vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges. Conclusion The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.

Da-Cheng-Qi decoction improves severe acute pancreatitis capillary leakage syndrome by regulating tight junction-associated proteins.

To investigate mechanisms underlying the effects of Da-Cheng-Qi decoction (DCQD) on severe acute pancreatitis (SAP) capillary leakage syndrome. In this study, a SAP rat model was established using retrograde perfusion of 5% sodium taurocholate into the biliopancreatic duct. The study included three randomized groups: control, SAP (modeling), and DCQD (via gavage at 2h pre-modeling and 2 and 4h post-modeling). HPLC was used to analyzed major components of DCQD. Pathological changes and capillary permeability in the rat pancreatic tissues were examined. mRNA levels of claudin 5, occludin, zonula occludin-1 (ZO-1), and junctional adhesion molecules (JAM-C) were assessed using qRT-PCR. Tight junction-associated protein expression was evaluated using immunofluorescence and Western blot analyses. Human umbilical vein endothelial cells (HUVECs) were used to investigate the mechanism m of DCQD. Serum levels of amylase, TNF-α, IL-1β, IL-2, and IL-6 were higher in the SAP group compared to the DCQD group (p < 0.05). DCQD treatment significantly attenuated rat pancreas damage (p < 0.05) and reduced tissue capillary permeability compared to the SAP group (p < 0.05). Claudin 5, occludin, and ZO-1 expression in the rat tissues was upregulated, but JAM-C was downregulated by DCQD treatment (p < 0.05). HUVEC permeability was improved by DCQD in a dose-time-dependent manner compared to the SAP group (p < 0.05). DCQD also upregulated claudin 5, occludin, and ZO-1 expression in vitro (p < 0.05). DCQD can improve capillary permeability in both in vivo and in vitro models of SAP by upregulating expression of claudin 5, occludin, and ZO-1, but not JAM-C.

The relationship between cardiac oxidative stress, inflammatory cytokine response, cardiac pump function, and prognosis post-myocardial infarction

This study delves into the potential connections between cardiac oxidative stress, inflammatory cytokine response, cardiac pump function, and prognosis in individuals following myocardial infarction. A total of 276 patients were categorized into two groups: the control group (n = 130) and the observation group (n = 146), based on the drug intervention strategies. The control group received standard drug treatment, while the observation group received early drug intervention targeting antioxidant and anti-inflammatory treatment in addition to standard treatment. Serum levels of inflammatory factors, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-9 (IL-6), were assessed using enzyme-linked immuno sorbent assay (ELISA) kits. The Forkhead Box Protein A2 (FOX2) reagent was used to determine the overall oxidation level. Left Ventricular End-Diastolic Diameter (LVEDD), Left Ventricular Ejection Fraction (LVEF), and End-Systolic Diameter (ESD) were measured using Doppler ultrasound. The observation group exhibited significantly reduced serum levels of TNF-α, IL-1β, and IL-6 compared to the control group (P < 0.05). Moreover, the observation group exerted lower total oxidation levels, OSI, EDD, and ESD compared to the control group (P < 0.05), while the LVEF and TAS levels in the observation group were higher than those in the control group (P < 0.05). Remarkably, the observation group experienced a significant reduction in the incidences of reinfarction, heart failure, arrhythmia, and abnormal valve function compared to the control group (P < 0.05). Decreased cardiac pump function and a more unfavorable prognosis were associated with elevated levels of cardiac oxidative stress and inflammatory factors (P < 0.05). Timely intervention with appropriate medications have a crucial effect in decreasing inflammatory marker levels, mitigating oxidative pressure, and enhancing cardiac pumping capacity and overall prognosis.

The relationship between serum resolvin D1, NLRP3, cytokine levels, and adolescents with first-episode medication-naïve major depressive disorder

BackgroundInflammation has become a critical pathological mechanism of Major Depressive Disorder (MDD). NLRP3 is a critical inflammatory pathway to maintain the immune balance. Recently, preclinical evidence showed that Resolvin D1 might potentially offer a new option for antidepressant treatment due to its protective effects through the inhibition of neuroinflammation. However, whether they have clinical value in the diagnosis and treatment evaluation of adolescent depression was unclear.MethodsForty-eight untreated first-episode adolescent patients with moderate to severe major depressive disorder, as well as 30 healthy adolescents (HCs, age and gender-matched), were enrolled for this study. Their ages ranged from 13 to 18 (15.75 ± 1.36) years. The patients were treated with fluoxetine for 6–8 weeks. HDRS-17 was used to evaluate the severity of depressive symptoms. Venous blood samples were collected at baseline for the two groups and at the time-point of post-antidepressant treatment for the patients. Serum concentrations of RvD1, NLRP3, IL-1β, IL-18, and IL-4 were measured by enzyme-linked immunosorbent assays (ELISA) pre- and post-fluoxetine treatment.ResultsSerum levels of RvD1 and anti-inflammatory cytokine IL-4 were significantly elevated in adolescents with MDD compared to healthy adolescents, but no significant difference in NLRP3, IL-1β, and IL-18 between the two groups. Meanwhile, RvD1 (positively) and IL-4 (negatively) were correlated with the severity of symptoms (HDRS-17 scores) after adjusting age, gender, and BMI. Interestingly, fluoxetine treatment significantly reduced the serum levels of RvD1, NLRP3, IL-1β, and IL-18 in MDD adolescents but increased the levels of IL-4 relative to baseline. Furthermore, we observed that serum levels of RvD1 might be an excellent distinguishing indicator for depression and healthy adolescents.ConclusionsOur study is the first to compare RvD1 and NLRP3 between adolescent MDD and HCs. Our findings of reactive increase of RvD1 in adolescent MDD comprised a novel and critical contribution. Our results showed the presence of inflammation resolution unbalanced in adolescents with MDD and indicated that RvD1 might be an ideal biomarker for diagnosing and treating adolescent MDD.

Relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration

Objective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group (n=24) and operation group (n=24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged (P=0.035), and the residence time in the target quadrant was reduced (P=0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1β, IL-6 and TNF-α between the two groups (all P>0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.

Level of interleukin 17 in inflammatory bowel disease and its relation with disease activity

BackgroundInflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder of the gastrointestinal tract (GIT).It results in progressive intestinal epithelium structural and functional damage that necessitates lifetime medication.Thereis imbalance in the production of T helper 1 (Th1), Th2 and Th17 cytokines. This plays a crucial role in the chronic inflammatory process and the defective immune response to pathogenic agents; thus promoting the recurrence of the disease.Our aim of this study was to detect serum IL-17 levels in IBD patients and its relation with disease activity.MethodsThis was a single center case control study, conducted at hepatology and gastroenterology unit, Mansoura specialized Medical Hospital, Egypt.Patients who were included were aged 18–65 years, diagnosed either Ulcerative Colitis (UC)or Crohn’s Disease (CD) based on previous colonoscopy.IBD activity was measured for UC using the MAYO score and CD using the CD activity index (CDAI). Fifty five patients were UC, 24 patients were CD, 21 patients were control.Patients who were excluded were under 15 years old, with history of GIT malignancy, or any serious comorbidities. Study protocol was approved by Institution Research Board (IRB) of Mansoura Medical College.All patients were subjected to full history taking, routine physical examination, colonoscopy and laboratory investigations including serum IL-17 levels by ELISA besides CBC, CRP, ESR and fecal calprotectin.ResultsSerum IL-17 level was increased significantly among UC; median (min-max) = 72(21–502)pg/ml, in CD 54.5(25–260) versus control 19 (14–35), P < 0.001.However, it was not correlated to the disease activity either Mayo score of UC or CDAI of CD.There was significant correlation to the extent of inflammation in UC affecting the colon (either proctosigmoiditis, left sided colitis or pan colitis), also to the type of CD (either inflammatory, stricturing or fistulizing) by P < 0.05.It was not correlated significantly with any of the IBD activity markers (CRP, ESR, or fecal calprotectin).Yet there was negative significant correlation with Hb level (r =-0.28, p = 0.005).There was not significant association between median serum level of IL-17 & duration of disease (P = 0.6).However, median IL-17 was higher among hospitalized cases than non-hospitalized (73 & 55, pg/ml respectively; p < 0.002). AUC was significantly differentiating between IBD and control group = 0.993 with the best-detected cut off point from curve 32 pg/ml yielding sensitivity of 97.5% and specificity of 95.2%.ConclusionSerum IL-17 increases in colonic inflammation significantly more than in control group, however its increase is not correlated to IBD activity.

Activation of the IL-6/STAT3 pathway contributes to the pathogenesis of membranous nephropathy and is a target for Mahuang Fuzi and Shenzhuo Decoction (MFSD) to repair podocyte damage

BackgroundPrimary membranous nephropathy (PMN) is an autoimmune glomerular disease. IL-6 is a potential therapeutic target for PMN. Previous clinical studies have demonstrated the effectiveness of Mahuang Fuzi and Shenzhuo Decoction (MFSD) in treating membranous nephropathy. However, the mechanism of action of MFSD remains unclear. MethodsSerum IL-6 levels were measured in patients with PMN and healthy subjects. The passive Heymann nephritis (PHN) rat model was established, and high and low doses of MFSD were used for intervention to observe the repair effect of MFSD on renal pathological changes and podocyte injury. RNA-seq was used to screen the possible targets of MFSD, and the effect of MFSD targeting IL-6/STAT3 was further verified by combining the experimental results. Finally, the efficacy of tocilizumab in PHN rats was observed. ResultsSerum IL-6 levels were significantly higher in PMN patients than in healthy subjects. These levels significantly decreased in patients in remission after MFSD treatment. MFSD treatment improved laboratory indicators in PHN rats, as well as glomerular filtration barrier damage and podocyte marker protein expression. Renal transcriptome changes showed that MFSD-targeted differential genes were enriched in JAK/STAT and cytokine-related pathways. MFSD inhibits the IL6/STAT3 pathway in podocytes. Additionally, MFSD significantly reduced serum levels of IL-6 and other cytokines in PHN rats. However, treatment of PHN with tocilizumab did not achieve the expected effect. ConclusionThe IL-6/STAT3 signaling pathway is activated in podocytes of experimental membranous nephropathy. MFSD alleviates podocyte damage by inhibiting the IL-6/STAT3 pathway.

The Effect of Granulocyte Colony-Stimulating Factor on Endometrial Receptivity of Implantation Failure Mouse.

The purpose of this study was to investigate the effect of G-CSF on the endometrial receptivity of implantation failure mice.Sixty female mice were treated mifepristone to establish an implant failure model. The treatment groups received different doses of G-CSF. Endometrial tissue and serum were collected on day 5 after mating. The abundance of pinopodes on the endometrium was observed by scanning electron microscopy. The expressions of LPAR3, COX2, and HOXA10 were detected by RT-qPCR and Western blotting. Serum levels of E2, P, VEGF, LIF, TNF-α and IL-10 were measured by ELISA. The expressions of VEGF, CD34, CD57, TNF-α, and IL-10 were assessed by immunohistochemistry. Immunofluorescence analysis was performed to determine the number of CD57, Treg, and Th17 cells.G-CSF increased implantation and pregnancy rates of mifepristone-induced implantation failure mice, with the most significant effect seen at the intermediate dose. G-CSF increased the serum levels of E2 and P, the abundance of endometrial pinopodes, and the level of LIF in the endometrium. It also promoted the expression of VEGF, HOXA10, LPAR3, and COX2. Moreover, G-CSF reduced the level of CD57 cells and the ratio of Th17/Treg cells in endometrium. G-CSF reduced the inflammatory factor TNF-α, but IL-10 did not change significantly.G-CSF can enhance embryo implantation rate and pregnancy rate and improve endometrial receptivity by attenuating degeneration of pinopodes, upregulating estrogen and progesterone, facilitating angiogenesis, maintaining immune cell homeostasis, and reducing the production of inflammatory cytokines in implantation failure mouse.

Deep Phenotyping the Anterior Urethral Stricture: Characterizing the Relationship Between Inflammation, Fibrosis, Patient History, and Disease Pathophysiology.

Anterior urethral stricture disease (aUSD) is a complex, heterogeneous condition that is idiopathic in origin for most men. This gap in knowledge rarely affects the current management strategy for aUSD, as urethroplasty does not generally consider etiology. However, as we transition towards personalized, minimally invasive treatments for aUSD and begin to consider aUSD prevention strategies, disease pathophysiology will become increasingly important. The purpose of this study was to perform a deep phenotype of men undergoing anterior urethroplasty for aUSD. We hypothesized that unique biologic signatures and potential targets for intervention would emerge based on stricture presence/absence, stricture etiology, and the presence/absence of stricture inflammation. Men with aUSD undergoing urethroplasty were recruited from one of 5 participating centers. Enrollees provided urethral stricture tissue and blood/serum on the day of surgery and completed patient-reported outcome measure questionnaires both pre- and postoperatively. The initial study had 3 aims: (1) to determine pediatric and adult subacute and repeated perineal trauma (SRPT) exposures using a study-specific SRPT questionnaire, (2) to determine the degree of inflammation and fibrosis in aUSD and peri-aUSD (normal urethra) tissue, and (3) to determine levels of systemic inflammatory and fibrotic cytokines. Two controls groups provided serum (normal vasectomy patients) and urethral tissue (autopsy patients). Cohorts were based on the presence/absence of stricture, by presumed stricture etiology (idiopathic, traumatic/iatrogenic, lichen sclerosus [LS]), and by the presence/absence of stricture inflammation. Of 138 enrolled men (120 tissue/serum; 18 stricture tissue only), 78 had idiopathic strictures, 33 had trauma-related strictures, and 27 had LS-related strictures. BMI, stricture length, and stricture location significantly differed between cohorts (P < .001 for each). The highest BMIs and the longest strictures were observed in the LS cohort. SRPT exposures did not significantly differ between etiology cohorts, with > 60% of each reporting low/mild risk. Stricture inflammation significantly differed between cohorts, with mild to severe inflammation present in 27% of trauma-related strictures, 54% of idiopathic strictures, and 48% of LS strictures (P = .036). Stricture fibrosis did not significantly differ between cohorts (P = .7). Three serum cytokines were significantly higher in patients with strictures compared to stricture-free controls: interleukin-9 (IL-9; P = .001), platelet-derived growth factor-BB (P = .004), and CCL5 (P = .01). No differences were observed in the levels of these cytokines based on stricture etiology. However, IL-9 levels were significantly higher in patients with inflamed strictures than in patients with strictures lacking inflammation (P = .019). Degree of stricture inflammation positively correlated with serum levels of IL-9 (Spearman's rho 0.224, P = .014). The most common aUSD etiology is idiopathic. Though convention has implicated SRPT as causative for idiopathic strictures, here we found that patients with idiopathic strictures had low SRPT rates that were similar to rates in patients with a known stricture etiology. Stricture and stricture-adjacent inflammation in idiopathic stricture were similar to LS strictures, suggesting shared pathophysiologic mechanisms. IL-9, platelet-derived growth factor-BB, and CCL5, which were elevated in patients with strictures, have been implicated in fibrotic conditions elsewhere in the body. Further work will be required to determine if this shared biologic signature represents a potential mechanism for an aUSD predisposition.

Shengxian decoction improves lung function in rats with bleomycin-induced idiopathic pulmonary fibrosis through the inhibition of PANoptosis

Ethnopharmacological relevanceShengxian decoction (SXD) is a classic Chinese medicinal formula that can effectively improve clinical symptoms and quality of life and delay disease progression in idiopathic pulmonary fibrosis (IPF) patients; however, the underlying mechanisms remain unclear. Aim of the studyThis study aimed to observe PANoptosis in bleomycin-induced IPF and to assess the efficacy and mechanism of action of SXD in the treatment of IPF. Materials and methodsFifty SD rats were randomly divided into the sham, IPF, IPF + pirfenidone (PFD), IPF + SXD-medium dose (SXD-M), and IPF + SXD-low dose (SXD-L) groups. Lung function analysis and microcomputed tomography imaging of the rats with IPF treated with oral pirfenidone or oral SXD for 28 days were performed. Hematoxylin and eosin (HE) staining and Masson's trichrome staining were used to observe pathological lung damage. Enzyme-linked immunosorbent assays (ELISAs) were used to determine the serum levels of IL-1β, IL-18, TNF-α, and IFN-γ. Pyroptosis, apoptosis, and necroptosis were assessed using TUNEL, TUNEL/caspase-1, and PI fluorescence staining, respectively. GSDMD, caspase-3, and MLKL were examined by immunohistochemistry. The expression of fibrin-, ZBP1-, pyroptosis-, apoptosis-, and necroptosis-related proteins in the lung tissue was determined by western blotting. ResultsSXD normalized lung function in rats with bleomycin-induced IPF and reduced serum inflammatory factor levels and lung tissue fibrosis. The underlying mechanism of action involves the inhibition of pyroptosis pathway proteins, such as NLRP3, caspase-1, cleaved caspase-1, and GSDMD; apoptotic pathway proteins, such as Bax, Bcl-2, cleaved caspase-3, and caspase-3; and necroptosis pathway proteins, such as RIPK1, RIPK3, p-MLKL and MLKL. These pathways are modulated by the PANoptosis initiator ZBP1. Notably, the efficacy of SXD is concentration dependent, with a medium dose exhibiting superior effectiveness compared to a low dose. ConclusionBleomycin induced PANoptosis in the lung tissue of rats with IPF. Additionally, SXD effectively delayed or reversed the early pathological changes in bleomycin-induced pulmonary fibrosis by inhibiting PANoptosis.

The impact of adipose fat tissue on the pathogenesis of crypto-glandular anal fistula.

&lt;b&gt;Indroduction:&lt;/b&gt; Cryptoglandular perianal fistula represents a prevalent benign anorectal condition, primarily addressed through surgical interventions, occasionally posing considerable therapeutic challenges. The associated decline in patient quality of life underscores the significance of effective management. However, the lack of a fully understood pathogenesis complicates the treatment approach. Recent research has proposed the involvement of adipose fat tissue in the inflammatory response and pathogenesis of cryptoglandular anal fistula.&lt;b&gt;Aim:&lt;/b&gt; The study aims to characterize the role of adipose fat tissue in the pathogenesis of cryptoglandular anal fistula, with a specific focus on understanding the potential involvement of proinflammatory cytokines in the development of chronic inflammation.&lt;b&gt;Materials and methods:&lt;/b&gt; This study involved the characterization of serum levels of inflammatory cytokines and adipose tissue hormones. A total of 35 samples from both simple and complex cryptoglandular perianal fistula cases were collected during surgical procedures.&lt;b&gt;Results:&lt;/b&gt; Serum levels of leptin, resistin, IL-1β, and IL-8 were significantly elevated in patients operated on due to complex cryptoglandular perianal fistula when compared to patients with simple fistula. Adiponectin was significantly lowered in samples from complex perianal fistula in comparison to simple fistula.&lt;b&gt;Conclusions:&lt;/b&gt; Complex perianal cryptoglandular fistula has a reduced level of anti-inflammatory adipokines i.e. adiponectin, and an increased level of proinflammatory resistin, leptin, IL-1β, and IL-8.

C-reactive protein lowers the serum level of IL-17, but not TNF-α, and decreases the incidence of collagen-induced arthritis in mice.

The biosynthesis of C-reactive protein (CRP) in the liver is increased in inflammatory diseases including rheumatoid arthritis. Previously published data suggest a protective function of CRP in arthritis; however, the mechanism of action of CRP remains undefined. The aim of this study was to evaluate the effects of human CRP on the development of collagen-induced arthritis (CIA) in mice which is an animal model of autoimmune inflammatory arthritis. Two CRP species were employed: wild-type CRP which binds to aggregated IgG at acidic pH and a CRP mutant which binds to aggregated IgG at physiological pH. Ten CRP injections were given on alternate days during the development of CIA. Both wild-type and mutant CRP reduced the incidence of CIA, that is, reduced the number of mice developing CIA; however, CRP did not affect the severity of the disease in arthritic mice. The serum levels of IL-17, IL-6, TNF-α, IL-10, IL-2 and IL-1β were measured: both wild-type and mutant CRP decreased the level of IL-17 and IL-6 but not of TNF-α, IL-10, IL-2 and IL-1β. These data suggest that CRP recognizes and binds to immune complexes, although it was not clear whether CRP functioned in its native pentameric or in its structurally altered pentameric form in the CIA model. Consequently, ligand-complexed CRP, through an as-yet undefined mechanism, directly or indirectly, inhibits the production of IL-17 and eventually protects against the initiation of the development of arthritis. The data also suggest that IL-17, not TNF-α, is critical for the development of autoimmune inflammatory arthritis.

Innate Responses to the Former COVID-19 Vaccine Candidate CVnCoV and Their Relation to Reactogenicity and Adaptive Immunogenicity.

Vaccines are highly effective at preventing severe coronavirus disease (COVID-19). With mRNA vaccines, further research is needed to understand the association between immunogenicity and reactogenicity, which is defined as the physical manifestation of an inflammatory response to a vaccination. This study analyzed the immune response and reactogenicity in humans, post immunization, to the former SARS-CoV-2 mRNA investigational vaccine CVnCoV (CV-NCOV-001 and CV-NCOV-002 clinical trials). Immunogenicity was investigated using whole-blood RNA sequencing, serum cytokine levels, and SARS-CoV-2-specific antibodies. The T cell responses in peripheral blood were assessed using intracellular cytokine staining (ICS) and high-dimensional profiling in conjunction with SARS-CoV-2 antigen-specificity testing via mass cytometry. Reactogenicity was graded after participants' first and second doses of CVnCoV using vaccine-related solicited adverse events (AEs). Finally, a Spearman correlation was performed between reactogenicity, humoral immunity, and serum cytokine levels to assess the relationship between reactogenicity and immunogenicity post CVnCoV vaccination. Our findings showed that the gene sets related to innate and inflammatory immune responses were upregulated one day post CVnCoV vaccination, while the gene sets related to adaptive immunity were upregulated predominantly one week after the second dose. The serum levels of IFNα, IFNγ, IP-10, CXCL11, IL-10, and MCP-1 increased transiently, peaking one day post vaccination. CD4+ T cells were induced in all vaccinated participants and low frequencies of CD8+ T cells were detected by ex vivo ICS. Using mass cytometry, SARS-CoV-2 spike-specific CD8+ T cells were induced and were characterized as having an activated effector memory phenotype. Overall, the results demonstrated a positive correlation between vaccine-induced systemic cytokines, reactogenicity, and adaptive immunity, highlighting the importance of the balance between the induction of innate immunity to achieve vaccine efficacy and ensuring low reactogenicity.