Higher Serum Levels Of IL-6 Research Articles

Interleukin17A: A Potential Target for Its Plausible Roles in the Pathogenesis of Idiopathic Epistaxis.

Introduction:It has been reported that inflammation may be a potential risk factor for the progression of epistaxis. Due to the major roles played by Th17 in the induction of inflammation, the present study aimed to assess the serum levels of Interleukin 17A (IL-17A) and IL-23, as the most important cytokines in the Th17 pathway, as well as IFN-, IL-4, and IL-10 serum levels, as regulatory cytokines for Th17 cells in patients with idiopathic epistaxis. Materials and Methods:The serum levels of IL-4, IL-10, IL-17A, IL-23, and IFN- were evaluated in 90 patients with idiopathic epistaxis and 90 healthy controls using enzyme-linked immunosorbent assay (ELISA) technique.Results:The obtained results pointed out that the serum levels of IL-17A and IL-10, but not IL-4 and IL-23, were significantly up-regulated, and IFN- serum levels were significantly down-regulated in patients with idiopathic epistaxis. Furthermore, female patients with epistaxis had higher IL-10 serum levels. Conclusions:As evidenced by the results of the present study, IL-17A is the main cytokine which participates in the pathogenesis of idiopathic epistaxis; moreover, in association with IL-10, it can be regarded as the suppressor of IFN- in patients.

High-fat diet caused renal damage in ApoE-/- mice via the activation of RAGE-mediated inflammation.

High-fat diet (HFD) is the primary cause of metabolic syndrome associated chronic kidney disease. This study aimed to investigate the pathogenesis of HFD-induced kidney injury. ApoE-/- mice were fed with HFD and kidney damage was examined. In addition, HK-2 human renal proximal tubular epithelial cells were treated with fructose and receptor of advanced glycation end products (RAGE) siRNA. The results showed that HFD increased body weight, blood glucose and insulin resistance in ApoE-/- mice. The kidney damage was associated with increased oxidative stress and strong staining of RAGE and NF-κB in kidney tissues, as well as high serum levels of TNF-α, IL-1β and IL-6. Western-blot analysis showed that HFD increased the levels of RAGE, p-IκBα, p-NF-κB, bax, caspase-3 and caspase-9 but decreased the levels of Bcl-2 in kidney tissues. In HK-2 cells, fructose promoted the secretion of TNF-α, IL-1β and IL-6 and increased the levels of RAGE, p-IκBα, p-NF-κB, bax, caspase-3 and caspase-9, but decreased the levels of Bcl-2. Moreover, RAGE siRNA could attenuate increased levels of p-IκBα, p-NF-κB, bax, caspase-3 and caspase-9 while restore decreased levels of Bcl-2 in fructose-treated HK-2 cells. In conclusion, HFD causes kidney injury by promoting oxidative stress, inflammation and apoptosis possibly through the activation of RAGE/NF-κB pathway.

Comparison of IL-6 and TNF-Alfa Serum Levels in Pre and Post Radiotherapy Nasopharyngeal Carcinoma Patients at the NTB Provincial Hospital

Nasopharyngeal carcinoma is often found in Asia, especially in South and Southeast China, with Indonesia being the fourth most common malignancy after breast cancer, cervical cancer, and lung cancer. NPC can generally be diagnosed only in the late stages, so it can increase morbidity and mortality. One of the recommendations for therapy for NPC is radiotherapy, but radiotherapy still fails due to a chronic inflammatory process involving several inflammatory cytokines such as IL-6 and TNF-Alfa. Cytokines play a role in various signaling pathways that can lead to increased proliferation, migration, invasion, angiogenesis, and inhibit apoptosis and even have an effect on resistance to therapy in many cancer cells, especially NPC. A good understanding of this pro-inflammatory cytokine, is expected to improve the prognosis in NPC patients in the future, knowing serum levels of IL-6 and TNF-Alfa pre and post radiotherapy. This is a preliminary study or literature study before the main study is conducted. Sources include scientific journals accessed through an online portal, namely NCBI. Poor prognosis in NPC patients with high serum levels of IL-6 and TNF-Alfa. The higher the levels of IL-6 and TNF-Alfa in post-radiotherapy NPC patients, the worse the condition is because these pro-inflammatory cytokines can activate various signaling pathways.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

IL-1 and IL-6 inhibition affects the neutralising activity of anti-SARS-CoV-2 antibodies in patients with COVID-19.

Severe Inflammatory Reactions in Mice Expressing a GFI1P2A Mutant Defective in Binding to the Histone Demethylase KDM1A (LSD1).

GFI1 is a DNA-binding transcription factor that regulates hematopoiesis by repressing target genes through its association with complexes containing histone demethylases such as KDM1A (LSD1) and histone deacetylases (HDACs). To study the consequences of the disruption of the complex between GFI1 and histone-modifying enzymes, we have used knock-in mice harboring a P2A mutation in GFI1 coding region that renders it unable to bind LSD1 and associated histone-modifying enzymes such as HDACs. GFI1P2A mice die prematurely and show increased numbers of memory effector and regulatory T cells in the spleen accompanied by a severe systemic inflammation with high serum levels of IL-6, TNF-α, and IL-1β and overexpression of the gene encoding the cytokine oncostatin M (OSM). We identified lung alveolar macrophages, CD8 T cell from the spleen and thymic eosinophils, and monocytes as the sources of these cytokines in GFI1P2A mice. Chromatin immunoprecipitation showed that GFI1/LSD1 complexes occupy sites at the Osm promoter and an intragenic region of the Tnfα gene and that a GFI1P2A mutant still remains bound at these sites even without LSD1. Methylation and acetylation of histone H3 at these sites were enriched in cells from GFI1P2A mice, the H3K27 acetylation being the most significant. These data suggest that the histone modification facilitated by GFI1 is critical to control inflammatory pathways in different cell types, including monocytes and eosinophils, and that a disruption of GFI1-associated complexes can lead to systemic inflammation with fatal consequences.

Increased levels of serum interleukin-10 are associated with poor outcome in adult hemophagocytic lymphohistiocytosis patients

BackgroundInterleukin-10 (IL-10) is an independent factor for predicting adverse outcomes in pediatric patients with hemophagocytic lymphohistiocytosis (HLH). However, little is known about its prognostic value in adult patients.MethodsThis single center retrospective study was conducted to explore the prognostic value of IL-10 in 101 adults newly diagnosed with HLH. The serum interleukin levels were quantitatively determined by chemiluminescence using cytokine profiling kits.ResultsSerum IL-10 levels were significantly increased in adult HLH patients. Elevated IL-10 levels was correlated with lower concentrations of hemoglobin (r = − 0.279, P = 0.005). IL-10 levels were significantly lower in patients with macrophage activation syndrome (MAS) than in those with infection-associated HLH (IAHS) and malignancy-associated HLH (MAHS) (P = 0.033, P = 0.012). Patients with MAS had relatively longer survival than those with IAHS and MAHS (P < 0.001). Univariate analysis indicated that hemoglobin < 8.2 g/dL, platelets < 40 × 109/L, lactate dehydrogenase ≥ 700 IU/L, albumin < 28 g/L, post-treatment ferritin > 1050 µg/L and IL-10 ≥ 129 pg/mL were poor prognostic factors for survival. However, multivariate analysis revealed that only high serum IL-10 levels (≥ 129 pg/mL) at diagnosis and high post-treatment ferritin levels (> 1050 µg/L) were independent risk factors for poor overall survival in adult HLH patients (HR: 4.087, 95% CI 2.064–8.090, P < 0.001; HR 3.814, 95% CI 2.042–7.126, P < 0.001, respectively).ConclusionsOur results suggest that higher serum IL-10 levels might be a prognostic marker in adult HLH patients.

Circulating Levels of the Interferon-γ-Regulated Chemokines CXCL10/CXCL11, IL-6 and HGF Predict Outcome in Metastatic Renal Cell Carcinoma Patients Treated with Antiangiogenic Therapy.

Simple SummaryWe have studied blood levels of cytokines/chemokines in patients with metastatic renal cell carcinoma treated with sunitinib or pazopanib, with the goal of identifying biomarkers that can predict efficacy and survival. We have found that high levels of CXCL10, CXCL11, HGF and IL-6 before treatment associate with poor prognosis in these patients. Moreover, these factors are correlated in patients with renal carcinoma, suggesting a coordinated expression and secretion. We have developed a prognostic signature including these factors that predicts very accurately prognosis. Our results may help defining better the group of renal cell carcinoma patients who may benefit from sunitinib/pazopanib.Sunitinib and pazopanib are standard first-line treatments for patients with metastatic renal cell carcinoma (mRCC). Nonetheless, as the number of treatment options increases, there is a need to identify biomarkers that can predict drug efficacy and toxicity. In this prospective study we evaluated a set of biomarkers that had been previously identified within a secretory signature in mRCC patients. This set includes tumor expression of c-Met and serum levels of HGF, IL-6, IL-8, CXCL9, CXCL10 and CXCL11. Our cohort included 60 patients with mRCC from 10 different Spanish hospitals who received sunitinib (n = 51), pazopanib (n = 4) or both (n = 5). Levels of biomarkers were studied in relation to response rate, progression-free survival (PFS) and overall survival (OS). High tumor expression of c-Met and high basal serum levels of HGF, IL-6, CXCL11 and CXCL10 were significantly associated with reduced PFS and/or OS. In multivariable Cox regression analysis, CXCL11 was identified as an independent biomarker predictive of shorter PFS and OS, and HGF was an independent predictor of reduced PFS. Correlation analyses using our cohort of patients and patients from TCGA showed that HGF levels were significantly correlated with those of IL-6, CXCL11 and CXCL10. Bioinformatic protein–protein network analysis revealed a significant interaction between these proteins, all this suggesting a coordinated expression and secretion. We also developed a prognostic index that considers this group of biomarkers, where high values in mRCC patients can predict higher risk of relapse (HR 5.28 [2.32–12.0], p < 0.0001). In conclusion, high plasma HGF, CXCL11, CXCL10 and IL-6 levels are associated with worse outcome in mRCC patients treated with sunitinib or pazopanib. Our findings also suggest that these factors may constitute a secretory cluster that acts coordinately to promote tumor growth and resistance to antiangiogenic therapy.

A single-center report of COVID-19 disease course and management in liver transplanted pediatric patients.

BackgroundIn 2019, SARS‐CoV‐2 causing COVID‐19 emerged. Severe COVID‐19 symptoms may evolve by virtue of hyperactivation of the immune system. Equally, immunocompromised patients may be at increased risk to develop COVID‐19. However, treatment guidelines for children following liver transplantation are elusive.MethodsAs a liver transplantation center, we diagnosed and followed up 10 children (male/female: 8/2) with a median age of 8.5 years (IQR: 5.2–11.0), with COVID‐19 post‐liver transplant between March 2019 and December 2020. COVID‐19 diagnosis was based on PCR test and or florid X‐ray findings compatible with COVID‐19 in the absence of other cause. We retrospectively collected clinical and laboratory data from electronic patient records following written consent from patients/parents.ResultsNine patients were diagnosed as definitive (PCR positive) with one patient being diagnosed as probable COVID‐19. Seven patients recovered without any support whereas three were admitted for non‐invasive oxygenation. Lymphopenia and/or high levels of serum IL‐6 were detected in four patients. Six patients mounted anti‐SARS‐CoV‐2 antibodies at median 30 days (IQR: 26.5–119.0) following COVID‐19 diagnosis. Antibiotic therapy, favipiravir, anakinra, and IVIG were used as treatment in 4,1,1 and 2 patients, respectively. Furthermore, we kept the tacrolimus with or without everolimus but stopped MMF in 2 patients. Importantly, liver allograft function was retained in all patients.ConclusionsWe found that being immunocompromised did not affect disease severity nor survival. Stopping MMF yet continuing with tacrolimus was an apt treatment modality in these patients.

POS0329 GASTROINTESTINAL INVOLVEMENT IN SYSTEMIC SCLEROSIS: PATHOGENETIC ROLE OF GUT MICROBIOME, CYTOKINES AND ADIPOKINES

Background:Gastrointestinal (GI) involvement is very common in patients with Systemic Sclerosis (SSc). The pathophysiology of GI manifestations has not yet been defined. Cell-mediated immunological reactions appear to lead to endothelial damage resulting in fibrosis. The risk of developing malnutrition reinforces the need to better understand GI pathophysiology in these patients.Objectives:The study aimed to evaluate GI symptoms (GIT 2.0) and malnutrition status (MUST) and to determine specific bacterial changes in gut microbiome by investigating the possible presence of positive hot spots in bacterial species in SSc patients and their potential role in the disease progression. We also evaluated serum levels of adipokines and cytokines involved in the pathogenesis of SSc and their role, in addition to gut microbiome, in predicting the onset of GI involvement and malnutrition in SSc patients.Methods:We enrolled 25 scleroderma patients (EULAR/ACR 2013 criteria). UCLA-SCTC GIT 2.0 questionnaire to evaluate GI symptoms and MUST to investigate the risk of malnutrition were used. Gut microbiome was analyzed and the samples were subjected to extraction for the 16S rRNA gene (Earth Microbiome Project and the NIH-Human Microbiome Project). The microbiome was investigated at phenotypic and genotypic level. Serum levels of cytokines and adipokines (adiponectin and leptin) were evaluated by ELISA.Results:79.9% of patients had GERD and 63.5% abdominal distension at GIT 2.0 questionnaires. 48% of patients had moderate risk of malnutrition (MUST=2) and 12% had high risk (MUST=3). Gut microbioma: 19 patients (76%) had low similarity and 11 (44%) low diversity compared to the healthy population. The prevailing enterotypes of gut microbiome was Bacteroides (80%) and Prevotella (20%). The genotypic evaluation showed a reduced concentration of: gluten-digesting (Lactobacillus); lactose-digesting (Faecalibacterium); vitamin K-producing (Enterococcus, Desulfovibrio and Veillonella); acetaldehyde-degrading bacteria. 24 patients (96%) showed a reduction in bacteria devoted to maintaining weight control (Bifidobacterium and Ruminococcus). The patients had an altered intestinal permeability with less mucolytic bacteria (Bacteroides) and reduced production of LPS (Enterobacter and Escherichia). Low levels of butyrate (Eubacterium and Clostridium), acetate and propionate were found for SCFA-producing bacteria. Potentially pathogenic bacteria were also investigated: Salmonella was found in 14 (56%), Klebsiella in 9 (36%) and Enterococcus Faecalis in 3 (12%) patients. 11 (44%) patients had elevated serum levels of IL10 and IL12; 4 (16%) had high value of leptin. Correlation was found in patients who had a reduced concentration of gluten-digesting bacteria and MUST. Elevated MUST was correlated with serological increase in IL17A and IFN-α. Serum levels of IL12 and IL10 were found to correlate with specific bacteria alterations: high concentration of acetaldehyde-producing bacteria and low levels of acetaldehyde-degrade bacteria (also correlated with high serum levels of IL6), mucolytic bacteria and producers of hydrogen sulphide, acetate and propionate. Finally, reduced levels of mucolytic bacteria and acetate producing bacteria correlated with high serum leptin levels.Conclusion:The relationship between the gut microbiome and SSc seems to be multifactorial. In our study genotypic changes of gut microbioma might play a role in damaging the permeability of the mucosa and increasing risk of malnutrition. The evaluation of gut microbiome and cytokine profile is probably going to be of value in the follow-up of SSc. However, further studies are needed to clarify the impact of GI dysbiosis on the immune system in SSc.

Impact of the Uncoupling Protein 1 on Cardiovascular Risk in Patients with Rheumatoid Arthritis.

Adiposity is strongly associated with cardiovascular (CV) morbidity. Uncoupling protein 1 (UCP1) increases energy expenditure in adipocytes and may counteract adiposity. Our objective was to investigate a connection between UCP1 expression and cardiovascular health in patients with rheumatoid arthritis (RA) in a longitudinal observational study. Transcription of UCP1 was measured by qPCR in the subcutaneous adipose tissue of 125 female RA patients and analyzed with respect to clinical parameters and the estimated CV risk. Development of new CV events and diabetes mellitus was followed for five years. Transcription of UCP1 was identified in 89 (71%) patients. UCP1 positive patients had often active RA disease (p = 0.017), high serum levels of IL6 (p = 0.0025) and were frequently overweight (p = 0.015). IL-6hiBMIhi patients and patients treated with IL6 receptor inhibitor tocilizumab had significantly higher levels of UCP1 compared to other RA patients (p < 0.0001, p = 0.032, respectively). Both UCP1hi groups displayed unfavorable metabolic profiles with high plasma glucose levels and high triglyceride-to-HDL ratios, which indicated insulin resistance. Prospective follow-up revealed no significant difference in the incidence of new CV and metabolic events in the UCP1hi groups and remaining RA patients. The study shows that high transcription of UCP1 in adipose tissue is related to IL6-driven processes and reflects primarily metabolic CV risk in female RA patients.

Исследование иммунопатологических процессов, связанных с развитием фиброза печени

The aim of this study was to determine the dependence of the course of liver fibrosis on the functional state of the immune system, in particular, on the imbalance of pro-inflammatory and anti-inflammatory immune reactions that are formed in patients during the development of the disease. The study included 30 patients with chronic liver diseases (18 patients with chronic hepatitis C (CHC) and 12 patients with alcoholic liver disease (ALD), 15 healthy individuals were the comparison group. Liver elastography (FibroScan) was used to evaluate liver stiffness and determine fibrosis stages according to METAVIR classification. The following cytokine levels were measured in the serum samples of the group: IL-1β, TNF-α, IL-6, IFN-γ, IL-2, IL-4, IL-8, VEGF and TGF-β. According to the data presented in this work, in patients with CHC and ALD, there was a statistically significant increase in serum levels of pro-inflammatory cytokines, namely: IL-1β, TNF-α, IFN-γ, IL-2, IL-6 and IL-8. Interestingly, elevated TGF-β values were found in patients with CHC, but not in patients with ALD. Significantly lower concentrations of VEGF were observed in both study groups. There was also a significant decrease in serum IL-4 in patients with CHC, whereas in patients with ALD such a decrease was not statistically significant. Serum IL-1β content was approximately equally elevated in the early and late stages of fibrosis. A sharp rise in serum TNF-α levels occurred in the early stages of fibrosis. In the later stages, the rise in the level was replaced by a sharp fall. However, the serum levels of TNF-α in the later stages of liver fibrosis still significantly exceeded control values. The serum levels of IFN-γ in patients significantly exceeded control values without changes in different stages of fibrosis. Relatively high levels of serum IL-2 and IL-6 were noted only in the later stages of the disease. In both groups of patients, a clear dependence of serum levels of IL-8 on the stage of fibrosis was revealed. Analysis of the data allows us to conclude that immune mechanisms play a significant role in the pathogenesis of degenerative liver diseases. Therefore further studies of the mechanism and role of immune factors is required to explore possible diagnostic and therapeutic applications.

Analysis of cytokine levels, T regulatory cells and serotonin content in patients with depression.

Alterations in peripheral serotonin concentrations and an imbalanced immune system have been reported in patients with depression. Cytokines and T regulatory (Treg) cells may play an important role in the development of depression. This study investigates the levels of cytokines and Treg cells, as well as the concentration of serotonin (5-HT) in the blood of 89 patients suffering from depression and 89 healthy participants between two acquisitions. We investigated the state of health before (T1) and after (T2) psychological and pharmacological therapy. Both cytokine (IL-6, IL-10, TNF-α, and INF-γ) and 5-HT levels in the blood were measured by enzyme-linked immunosorbent assays. The levels of CD4+ CD25+ Treg cells were determined by flow cytometric analysis. Patients with depression showed significantly higher serum levels of IL-6 and INF-γ, no altered serum levels of IL-10 and TNF-α, and decreased platelet and serum 5-HT levels compared with healthy participants at the first acquisition. In addition, the symptoms of depression and anxiety, the TNF-α level, and the amount of CD4+ CD25+ cells in the blood were decreased from the first to the second acquisition. Further, a correlation between IL-6 and platelet 5-HT has been observed in patients. An imbalance of the immune system in patients with depression and an association of the serotonergic system and cytokines were observed. These results indicate that the development of depression might be related to several interacting proteins, including cytokines and 5-HT, and the treatment affects imbalances of these factors.

Andrographolide Treatment Lessens Localized, Systemic Inflammation and Improves Other Pathophysiological Traits in a Mouse Model of Gulf War Illness

Gulf War Illness (GWI) is a chronic multi-symptom disorder that affected almost one-third of the deployed veterans during the first Persian Gulf War (1990-91). Symptoms include gastrointestinal disturbances, chronic fatigue, cognitive deficiencies, and neuroinflammation. Our group has recently shown a series of different therapeutic strategies that span oral butyrate, anti-viral drug Ribavirin, and TLR4 antagonist Sparstolonin B effectively improving outcomes to murine GWI-linked symptoms. Andrographolide (AG), a labdane diterpenoid produced by the plant Andrographis paniculata, exerts numerous beneficial effects in various cell types. Adult C57BL/6J mice were exposed to the GWI chemicals (GWC) pyridostigmine bromide and permethrin for a week (GWT group) and simultaneously treated with AG (GWT+AG group). In our previous report, virome dysbiosis showed a strong association with GWI inflammation. Next-Gen Sequencing data showed both virome richness and Shannon diversity were markedly altered in GWT+AG mice than GWT mice. The observed increased relative abundance of Siphoviridae, Myoviridae, and decreased Microviridae abundance in the GWT group was reversed by AG treatment, referring to a restored gut environment. Gut leaching marked by decreased Occludin expression and increased Claudin2 expression was reversed by AG treatment, a likely consequence of AG induced decrease in TLR4 and TLR7 expression. AG administration restored gut barrier integrity, decreased TLR4 activation, NFκb phosphorylation, and gut inflammation. Furthermore, systemic inflammation in GWT mice, evidenced by the high level of serum IL-1β and IL-6, was found to be decreased in GWT+AG mice. Blood-brain barrier (BBB) integrity loss and resulting microglial activation, a common feature of GWI murine pathology were reversed by AG treatment. AG restored dysfunctional BBB by enhancing tight junction protein Claudin5 expression as well as decreased microglial activation. Also, AG administration led to high brain-derived neurotrophic factor (BDNF) expression in the frontal cortex, a molecule with a pronounced role in synaptic plasticity and neuronal regeneration. In summary, these results explicitly imply that AG played a key role in decreasing GWI-associated intestinal, systemic, and neuroinflammation whereas it also improved intestinal barrier and BBB integrity in the GWI mouse model.

Innate immune profiling discriminates between liver regeneration and liver failure following partial hepatectomy

Abstract Post-hepatectomy liver failure is a major complication following liver resection and while the basic mechanisms are not well understood, limited regeneration of the remnant tissue contributes to its development. Using an established murine model of 70% partial hepatectomy, we studied the innate immunological profile associated with liver regeneration and liver failure. Following partial hepatectomy, there is a significant increase in circulating CD11b+ myeloid derived cells from (52±10 to 70±12 p&amp;gt;0.01). Further characterization of the CD11b+ cells revealed three different subpopulations: Gr-1hiF4/80, Gr-1hiF4/80+, and Gr-1loF4/80+. Liver failure was accompanying with markedly prolonged and increased mobilization and liver infiltration of activated CD11b+ cells (6±2% on day 0 to 55±12% on day 1 p&amp;gt;0.001). Specifically, the CD11b+Gr-1hiF4/80− cells identified as neutrophils were predominantly increased in these mice from (25±5% to 80±10% p&amp;gt;0.001) on day 1. And persistently remained high until day 7. We also found high IL-6 serum levels in these mice (300±150pg/mL) on day 1. The other CD11b+ cell populations, including Gr-1hiF4/80+ and Gr-1loF4/80+ cells, were markedly reduced in peripheral blood of mice with impaired liver regeneration. In contrast, all CD11b+ populations rapidly recovered to normal levels within 2 days in mice showing normal liver regeneration. In conclusion, following partial hepatectomy, significantly prolonged infiltration of CD11b+ neutrophils and marked reduction of other CD11b+ populations are a hallmark of liver failure. Thus, controlling neutrophil infiltration/activation may help ease recovery from the surgical procedure and improve liver regeneration after partial liver resection.

Association of Serum Vitamin D with Serum Cytokine Profile in Patients with Knee Osteoarthritis.

The role of vitamin D in the pathogenesis of osteoarthritis (OA) is not well understood. In this study, we aimed to investigate the association of serum vitamin D with the serum cytokine profile in patients with primary knee OA. In a cross-sectional study, 116 patients with radiologic diagnosis of grade I to III knee OA were included. The study population included 79 (75.9%) females and 25 (24.1%) males with a mean age of 55.1 ± 9.6 years. The serum concentration of IL-6, IL-8, TNF-α, IL-4, IL-10, IL-13, and vitamin D were assessed using an enzyme-linked immunosorbent assay. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used for the assessment of patient's reported disability associated with knee OA. Serum vitamin D status was deficient, insufficient, and sufficient in 18 (15.5%), 63 (54.3%), 35 (30.2%) patients, respectively. Higher levels of serum IL-6 were observed in patients with vitamin D deficiency (P = 0.022). The mean serum vitamin D level was not associated with OA grade (P = 0.88) and WOMAC scores of the patients (P = 0.67). Serum IL-6 level was significantly associated with both OA grade and WOMAC scores of the patients (P < 0.001 and P = 0.001, respectively). The vitamin D status was not significantly associated with the serum levels of other evaluated cytokines. Vitamin D deficiency in knee OA seems to be associated with a higher release of IL-6. Therefore, vitamin D supplementation could reduce the disease burden by controlling the IL-6 release.

Associations of Serum Cytokine Levels and Interleukin-6-572C/G Polymorphism with Myelin Damage in Chinese Children with Autism Spectrum Disorder

Increasing evidence suggests that immunological disturbances and abnormalities in axonal myelination are involved in the pathophysiology of autism spectrum disorder (ASD). The present study aimed to determine the role of cytokines in myelin damage in Chinese children with ASD and the role of cytokine dysregulation, myelin damage, and cytokine polymorphisms in ASD in Chinese children. The present case-control study included 98 ASD subjects and 252 typically developing (TD) controls; the levels of serum cytokines and myelin basic protein (MBP) were determined using enzyme-linked immunosorbent assay. Cytokine polymorphisms were genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Autistic clinical manifestations were assessed by the Childhood Autism Rating Scale (CARS). The results showed that serum levels of interleukin (IL)-1β, IL-2R, IL-6, IL-8, and MBP were higher in children with ASD compared with those in TD children. In individuals with ASD, serum MBP level was significantly positively associated with the CARS total score, and serum levels of IL-1β, IL-2R, IL-6, and MBP demonstrated positive correlations. The data identified IL-6*MBP as a factor that influenced the risk of ASD, and IL-2R*MBP was identified as a factor that influenced symptom severity, which influenced auxiliary diagnosis of ASD. The presence of the interleukin-6-572CC genotype was associated with significantly higher serum levels of IL-6 and MBP but did not influence the risk and symptom severity of ASD. Therefore, the results suggested inflammatory responses and myelin damage in Chinese children with ASD. Cytokine dysregulation influenced myelin damage in ASD; moreover, the interactions of the cytokines and myelin damage influenced the risk and symptom severity of ASD. The IL-6-572C/G genotypes may be associated with myelin damage in ASD by influencing the circulating level of IL-6.

Crosstalk between proteinuria, plasma oxalic acid and inflammation in glomerulonephritis patients: an exploratory study

Abstract. In the present exploratory cross-sectional cohort study, we evaluated whether plasma and urine oxalate concentrations in patients with primary glomerulonephritis depend not only on the glomerular filtration rate but also on the proteinuria level and influence the inflammatory response.&#x0D; Methods. We enrolled 100 participants, including 76 patients with glomerulonephritis having chronic kidney disease stage (CKD) 1–3b (69.7% of them with nephrotic syndrome) and 24 healthy volunteers. We excluded patients with diabetes, cardiovascular disease and those with glomerulonephritis with an estimated GFR (eGFR) &lt; 30 mL/min/1.73 m2. In addition to routine hematological and biochemical tests, plasma oxalate concentration, urinary oxalate excretion, and serum interleukin (IL)-6 and monocyte chemoattractant protein-1 (MCP-1) levels were assessed in all study participants.&#x0D; Results. We observed that plasma oxalic acid concentration was significantly higher in patients with glomerulonephritis (19.0 [5.9–45.2] µmol/L) than in healthy volunteers (5.5 [3.8–7.3] µmol/L, p &lt; 0.0001). Moreover, nephrotic proteinuria was significantly associated with plasma oxalic acid elevation independent of the patients’ age, sex, glomerular filtration rate, and body mass index (odds ratio = 1.42, 95% confidence interval = 1.13–1.77, p = 0.002). In turn, the increased plasma oxalic acid concentration was associated with high levels of serum IL-6 and MCP-1, which may be cardiovascular risk factors in patients with primary glomerulonephritis.&#x0D; Conclusions. Nephrotic proteinuria was significantly associated with the elevation of plasma oxalic acid concentration and hyperoxaluria in glomerulonephritis patients with CKD stages 1–3b. Plasma oxalate at least partly promotes inflammation, which may be a cardiovascular risk factor in patients with glomerulonephritis in the early stages of CKD. Future studies should recruit at least 156 participants to confirm our preliminary results, validate nephrotic proteinuria as a risk factor for oxalate metabolism violation or determine the role of impaired oxalate homeostasis in clinical outcomes in patients with glomerulonephritis.

Expression of Programmed Cell Death 1 (PD-1) as a Marker of T-Cell Exhaustion and Its Correlation with Interleukin-10 Serum Level in Patients with COVID-19

Coronavirus disease 2019 (COVID-19), which is a major global concern, is characterized by a progressive disease pattern involving diverse host immune responses. Programmed cell death marker-1(PD-1) expression, a critical checkpoint for T cell exhaustion, can be modulated by interleukin-10, which also mediates apoptotic T cell cytopenia. We aimed to measure the level of PD-1 expression and to investigate its correlation with IL-10 serum levels in modulating T cell effector function, correlating the results with the level of severity of the disease. This study involved 40 patients with COVID-19 and 20 healthy controls. Using flow cytometry, the expression of PD-1 was determined on CD8+ T lymphocytes and CD4+ T lymphocytes. ELISA was used to determine the levels of IL-10 in the serum. We found a remarkable decrease in T cell counts with functionally exhausted surviving T cells in the patient groups, especially in patients with severe disease. PD-1 expression increased significantly in CD4+, CD8+, and total T cells, showing a higher expression in CD8+ T cells. The patient groups had significantly higher serum IL-10 levels than the control group. The ROC analysis demonstrated the predictive role of IL-10 levels in disease severity (65% sensitivity, 80% specificity, and AUC = 0.806). IL-10 serum levels and PD-1 expression in total T cells were positively correlated, suggesting that IL-10 participates in T cell exhaustion.

Factors impacting Catecholamines in Caregivers of Patients with Dementia

Background: Caregivers of dementia patients have significantly higher levels of serum IL-6 and CRP compared to non-caregivers, and the accumulation of everyday stressors reportedly promotes the induction of inflammatory markers. However, few studies have identified factors that affect catecholamine levels in caregivers who experience a combination of physical and mental stress from caregiving.Purpose: This study aimed to identify physical factors that impact catecholamine levels in caregivers of dementia patients.Methods: Participants were elderly caregivers living together with elderly Alzheimer’s-type dementia patients. We performed logistic regression analysis, with levels of adrenaline, noradrenaline, and dopamine (indicators of catecholamine) as dependent variables.Results: Caregiver BMI had a significant impact on adrenaline levels (OR: 0.792; 95%CI: 0.654-0.960) and noradrenaline levels (OR: 1.210; 95%CI: 1.009-1.451), whereas age had a significant impact on dopamine levels (OR: 1.162; 95%CI: 1.019-1.324).Discussion: While caregiver BMI significantly impacted adrenaline and noradrenaline levels, the mechanism underlying these relationships is unclear. One possibility is that obesity (BMI) and a rise in sympathetic nerve activity contributed to hypertension. Our findings suggest that chronic stress in elderly caregivers may potentially impair the dopaminergic activation system in the brain.Conclusion: There is a need to identify factors which increase BMI in caregivers. Future studies aimed at gaining a better understanding of the lifestyle habits of caregivers and intervention studies aimed at reducing their BMI are warranted.

IL-6 and IL-10 are associated with disease severity and higher comorbidity in adults with COVID-19

AimCOVID-19 pandemic has caused extensive burden on public life and health care worldwide. This study aimed to assess circulating levels of inflammatory cytokines in adult patients who were hospitalized with COVID-19 and stratified according to age (older or younger than 65 years) aiming to explore associations between these markers of inflammation and comorbidities. MethodsThis was a cross-sectional study of 142 COVID-19 patients consecutively admitted to the University Hospital of the Federal University of São Carlos, from July to October 2020. Sociodemographic data, chronic comorbidities, and baseline NEWS2 and SOFA for clinical deterioration were obtained at hospital admission. Serum levels of inflammatory cytokines were determined by flow cytometry. ResultsOlder adults with COVID-19 had higher serum levels of IL-6 and IL-10 as compared to those under 65 years of age (p < 0.001 and p = 0.003, respectively). IL-10 was independently associated with age (p = 0.04) and severity of the disease (p = 0.05), whereas serum levels of IL-6 were not directly associated with age (p = 0.5). The comorbidity index seems to be the main responsible for this, being significantly associated with IL-6 levels among those aged 65 and over (p = 0.007), in addition to the severity of the disease. ConclusionsHigher serum levels of IL-6 and IL-10 are associated with the severity of the disease and a higher comorbidity index among adults aged 65 and over with COVID-19. This should raise awareness of the importance of comorbidity index, rather than age, during risk stratification.