Elevated Serum Interleukin-6 Levels Research Articles

Inflammatory biomarkers and frailty transitions in older adults with cancer: Findings from a national cohort study.

e13772 Background: Approximately 67% of cancer survivors were aged 65 or older in the U.S.; they face a heightened risk of frailty, as both cancer and anti-cancer treatment impose additional stressors on the older adults’ physiological reserves. Inflammatory biomarkers such as serum C-reactive protein (CRP) and Interleukin-6 (IL-6) levels were associated with frailty. However, the role of inflammatory biomarkers on the transitions of frailty states remains unclear. This study aimed to describe transitions between frailty states and death and quantify the predictive effect of inflammatory biomarkers on transitions. Methods: We used data from the National Health and Aging Trends Study (NHATS) from 2017 to 2022. A total of 1,219 older cancer survivors (>67 years) were included. Frailty was assessed annually using the Fried Frailty Phenotype (exhaustion, low physical activity, shrinking, low walking speed, and weakness) to categorize participants as “non-frail,” “pre-frail,” and “frail.” Inflammatory biomarkers were obtained via dried blood spots at baseline (2017). Plasma-equivalent values of CRP and IL-6 were used. Covariates included sex, age category, race, education level, marital status, obesity, and number of comorbidities. We defined four states that included three frailty states (non-frail, pre-frail, and frail) and an absorbing state of death. The multi-state Markov models were performed to capture possible transitions between frailty states and examine the effect of CRP and IL-6 on the five main transitions between states (non-frail to pre-frail, pre-frail to non-frail, pre-frail to frail, frail to pre-frail, frail to death). Results: At baseline, 25.27% were non-frail, 52.34% were pre-frail, and 22.40% were frail. During the follow-up time of 5 years, 1,396 transitions were observed, with 950 (68.05%) progressions (or to death) and 446 (31.95%) reversals. For participants who were non-frail, they were highly likely to develop pre-frailty (transition intensity=0.63). For participants with pre-frailty, progression to frailty was a little more likely than recovery to non-frailty (0.25 vs 0.21). Once entering the frail state, the likelihood of death outweighed that of recovery (0.30 vs 0.28). A higher level of CRP or IL-6 was associated with frailty progression (non-frail to pre-frail and frail to death), while a lower level of CRP or IL-6 was associated with recovery of frailty (pre-frail to non-frail and frail to pre-frail). Conclusions: This study is the first to investigate the longitudinal relationship between inflammatory biomarkers and frailty transitions in older cancer survivors using a nationally representative survey dataset. Our findings outlined potential transitions between frailty states and death, highlighting the role of elevated serum CRP and IL-6 levels on the increased risk of frailty progression and reduced risk of frailty recovery over 5 years.

The NLRP3 inflammasome is essential for IL-18 production in a model of macrophage activation syndrome.

Hyperinflammatory disease is associated with an aberrant immune response resulting in cytokine storm. One such instance of hyperinflammatory disease is known as macrophage activation syndrome (MAS). The pathology of MAS can be characterised by significantly elevated serum levels of interleukin (IL)-18 and interferon (IFN)-γ. Given the role for IL-18 in MAS, we sought to establish the role of inflammasomes in the disease process. Using a murine model of CpG-DNA induced MAS, we discovered that the expression of the NLRP3 inflammasome was increased and correlated with IL-18 production. Inhibition of the NLRP3 inflammasome, or downstream caspase-1, prevented MAS-mediated upregulation of plasma IL-18 but interestingly did not alleviate key features of hyperinflammatory disease including hyperferritinaemia and splenomegaly. Furthermore IL-1 receptor blockade with IL-1Ra did not prevent the development of CpG-induced MAS, despite being clinically effective in the treatment of MAS. These data demonstrate that in the development of MAS, the NLRP3 inflammasome was essential for the elevation in plasma IL-18, a key cytokine in clinical cases of MAS, but was not a driving factor in the pathogenesis of CpG-induced MAS.

Evaluation of the Diagnostic Utility of Selected Serum Adipokines and Cytokines in Subjects with MASLD-A Pilot Study.

Excess adipose tissue, particularly of the visceral type, triggering chronic low-grade inflammation and altering its secretory profile, is a contributing factor to the initiation and progression of metabolic dysfunction-associated steatotic liver disease (MASLD). This study aimed to compare the levels of selected adipokines and cytokines in individuals with normal weight and obesity, assessing their potential for diagnosing MASLD and establishing a cutoff point for body fat content associated with hepatic steatosis development. The research involved 99 participants categorized by body mass index and MASLD presence, undergoing body composition analysis, liver elastography, biochemical tests, and evaluation of adipokines and cytokines in serum. The results indicated elevated IL-6 (interleukin 6) serum levels in individuals with obesity with MASLD compared to the normal-weight group without MASLD. The multivariate regression analysis demonstrated a connection between hepatic steatosis and total adipose tissue content, VAT (visceral adipose tissue), VAT/SAT (subcutaneous adipose tissue) ratio, HOMA-IR (homeostasis model assessment of insulin resistance), IL-6, Il-1β (interleukin 1β), and MMP-2 (matrix metalloproteinase 2). Among the adipokines and cytokines examined in this study, interleukin 6 was the strongest predictor of MASLD regardless of gender. In addition, an association between the development of hepatic steatosis and higher serum IL-1β levels and higher adipose tissue was observed in women. However, further studies on a larger group of patients are needed to consider the use of these cytokines as markers of MASLD. The HOMA-IR index demonstrated potential diagnostic utility in identifying hepatic steatosis.

Cryptogenic non-cirrhotic HCC: Clinical, prognostic and immunologic aspects of an emerging HCC etiology

The incidence of hepatocellular carcinoma (HCC) in non-cirrhotic livers is rising significantly, but clear risk factors for screening remain elusive. This study sought to characterize non-cirrhotic HCC etiologies. HCC cases from 2009 to 2020 in a Dutch referral center were examined, revealing 371 out of 1654 cases (22%) as non-cirrhotic. Notably, the incidence of non-cirrhotic HCC increased by 61% in the time frame between 2009 and 2020. Interestingly 39% of non-cirrhotic HCC cases had cryptogenic origins. Cryptogenic non-cirrhotic HCC exhibited similarities with non-cirrhotic NAFLD HCC, but displayed advanced tumor stages, lower surgical rates, and a more frequent presence of symptoms, which substantiated in poor survival rates. Advanced cryptogenic non-cirrhotic HCC stages exhibited elevated serum interleukin-6 levels compared to non-cirrhotic HCC with defined etiologies. Comparative analysis encompassing cryptogenic and NAFLD non-cirrhotic HCC cohorts and controls unveiled comparable circulating immune biomarker profiles and PNPLA3 polymorphisms. To conclude, the primary etiology of non-cirrhotic HCC in our cohort has not defined risk factors. This cryptogenic variant exhibits distinct traits, such as advanced tumors and increased symptoms, and most resemble burned-out NAFLD. Understanding this HCC variant is crucial for improving screening and management strategies.

Metabolomics of interventional effects of Coptidis Rhizoma and its processed products on oral ulcer due to excess heat in rats

Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q/TOF-MS) was employed to examine the impact of Coptidis Rhizoma(CR) and its processed products on the metabolism in the rat model of oral ulcer due to excess heat and to compare the effectiveness of CR and its three products. Male SD rats were randomly allocated to the sham-operation(Sham), model(M, oral ulcer due to excess heat), CR, wine/Zingiberis Rhizoma Recens/Euodiae Fructus processed CR(wCR/zCR/eCR), and Huanglian Shangqing Tablets(HST) groups. Except the Sham group, the other groups were administrated with Codonopsis Radix-Astragali Radix decoction by gavage for two consecutive weeks. The anal temperature and water consumption of rats were monitored throughout the modeling period of excess heat. Following the completion of the modeling, oral ulcer was modeled with acetic acid. Hematoxylin-eosin(HE) staining was employed to observe the mucosal pathological changes in oral ulcer. A colorimetric assay was employed to determine the serum level of glutathione peroxidase(GSH-Px). Enzyme-linked immunosorbent assay(ELISA) was conducted to determine the levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), interleukin-1β(IL-1β), superoxide dismutase(SOD), and malondialdehyde(MDA) in the serum. The non-targeted metabolomics analysis based on UPLC-Q/TOF-MS was conducted on the serum samples. Metabolic profiles were then built, and the potential biomarkers were screened by principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA). The Mev software was used to establish a heat map and conduct cluster analysis on the quantitative results of the markers. The online databases including MBRole, KEGG, and MetaboAnalyst were used for pathway enrichment analysis and metabolic network building. The experimental results showed that the modeling led to pathological damage to the oral mucosa, elevated serum levels of TNF-α, IL-6, IL-1β, and MDA, and lowered levels of SOD and GSH-Px in rats. The drug administration recovered all the indices to varying extents, and wCR exhibited the best performance. Non-targeted metabolomics identified 48 differential metabolites including 27 metabolites in the positive ion mode and 21 metabolites in the negative ion mode. Five enriched pathways were common, including glycerophospholipid metabolism, linoleic acid metabolism, and tyrosine metabolism. Conclusively, CR and its three processed products could alleviate the inflammation and oxidative stress injury in rats suffering from oral ulcers due to excess heat by regulating lipid and amino acid metabolism. Notably, wCR demonstrated the most significant therapeutic effect.

Increased Serum Interleukin 10 Levels Are Associated with Increased Disease Activity and Increased Risk of Anti-SS-A/Ro Antibody Positivity in Patients with Systemic Lupus Erythematosus.

To evaluate the association between serum IL-10 levels and autoantibodies, disease activity and organ involvement in systemic lupus erythematosus (SLE) patients. We studied 200 SLE patients and 50 controls. We analyzed organ involvement, disease activity, serum IL-10 and interleukin-6 (IL-6) levels, and antinuclear and antiphospholipid antibody profiles. Serum IL-10 and IL-6 levels were higher in SLE patients than in controls (all p < 0.00001). Serum IL-10 levels were positively correlated with IL-6 (p < 0.00001), CRP (p < 0.00001), fibrinogen (p = 0.003), and ESR (p < 0.00001), and negatively correlated with hemoglobin (p = 0.0004) and lymphocytes (p = 0.01). Serum IL-6 levels were positively correlated with CRP (p < 0.00001), fibrinogen (p = 0.001), and ESR (p < 0.00001); and negatively correlated with hemoglobin (p = 0.008) and lymphocytes (p = 0.03). Elevated serum IL-10 levels were associated with an increased risk of anti-SS-A/Ro antibody positivity (p = 0.03). Elevated serum IL-6 levels were associated with an increased risk of heart (p = 0.007) and lung (p = 0.04) involvement. In SLE patients, increased serum IL-10 levels were associated with increased disease activity and risk of anti-SS-A/Ro antibody positivity.

Critically-Elevated Interleukin-6 (IL-6): A Prognostic Biomarker for Post-Acute Sequelae of COVID-19 (PASC)? (P2-7.001)

<h3>Objective:</h3> To investigate whether IL-6 is a prognostic factor in SARS-CoV-2 related encephalopathy in development of PASC. <h3>Background:</h3> It is currently unclear whether elevated IL-6 can be a prognostic factor in development of PASC. <h3>Design/Methods:</h3> A retrospective chart review was performed on hospitalized SARS-CoV-2 infection encephalopathy patients during March-May of 2020 at an urban tertiary care center. Patients were divided into two subgroups according to critically elevated (CE-IL6) vs non-critically elevated (NCE-IL6) initial serum IL-6 levels (as defined as &gt;86.95 pg/mL as per previous literature). Charts were analyzed for patients who had follow-up between 4 weeks and 1 year from initial visit to analyze subsequent development of new or persisting respiratory, cardiac, renal, or neurological symptoms to determine incidence of PASC. <h3>Results:</h3> Of 57 encephalopathy SARS-CoV-2 infection patients reviewed, 29 and 28 patients were found to be in the CE-IL6 and NCE-IL6 groups, respectively (average serum IL-6 level of 543.73 pg/mL vs 47.85 pg/mL, p = 0.0039). Among the CE-IL6 group, 68.97% patients had follow-up at least 4 weeks post admission vs 64.29% in NCE-IL6 group (p &gt; 0.05), with an average total follow up time of 529.89 days post initial admission in CE-IL6 and 520.31 days for NCE-IL6 (p &gt; 0.05). In the follow-up CE-IL6 group, 90% reported any one of the PASC symptoms whereas in the follow-up NCE-IL6 group, 22.22% reported any PASC symptoms (RR = 4.05, 95% CI [1.69–9.73], p = 0.0018). 12 patients received Tocilizumab (IL-6 inhibitor) in the CE-IL6 group and only 58.33% of them developed PASC. <h3>Conclusions:</h3> Encephalopathic patients who had critically elevated IL-6 serum levels on initial hospital admission for SARS-CoV-2 infection may be at increased risk of developing of PASC which could be attenuated by IL-6 inhibitor. Work in progress to confirm these findings by expanding sample size, increasing follow up time and stratifying for confounding factors. <b>Disclosure:</b> Mr. Trivedi has nothing to disclose. Mr. Jaffry has nothing to disclose. Ms. Faiz has nothing to disclose. Mr. Ors has nothing to disclose. Mr. Mandava has nothing to disclose. Mr. Jaffry has nothing to disclose. Miss Shaikh has nothing to disclose. Dr. Surathi has nothing to disclose. Dr. Tofade has nothing to disclose. Mr. Huff has nothing to disclose. Dr. Redko has nothing to disclose. Dr. Souayah has received publishing royalties from a publication relating to health care.

Maternal pre-eclampsia serum increases neurite growth and mitochondrial function through a potential IL-6-dependent mechanism in differentiated SH-SY5Y cells.

Introduction: Pre-eclampsia (PE) is a common and serious hypertensive disorder of pregnancy, which affects 3%-5% of first-time pregnancies and is a leading cause of maternal and neonatal morbidity and mortality. Prenatal exposure to PE is associated with an increased risk of neurodevelopmental disorders in affected offspring, although the cellular and molecular basis of this increased risk is largely unknown. Methods: Here, we examined the effects of exposure to maternal serum from women with PE or a healthy uncomplicated pregnancy on the survival, neurite growth and mitochondrial function of neuronally differentiated human SH-SY5Y neuroblastoma cells, which are commonly used to study neurite growth. Neurite growth and mitochondrial function are two strongly linked neurodevelopmental parameters in which alterations have been implicated in neurodevelopmental disorders. Following this, we investigated the pleiotropic cytokine interleukin-6 (IL-6) levels as a potential mechanism. Results: Cells exposed to 3% (v/v) PE serum for 72h exhibited increased neurite growth (p < 0.05), which was validated in the human neural progenitor cell line, ReNcell® VM (p < 0.01), and mitochondrial respiration (elevated oxygen consumption rate (p < 0.05), basal mitochondrial respiration, proton leak, ATP synthesis, and non-mitochondrial respiration) compared to control serum-treated cells. ELISA analysis showed elevations in maternal IL-6 in PE sera (p < 0.05) and placental explants (p < 0.05). In support of this, SH-SY5Y cells exposed to 3% (v/v) PE serum for 24h had increased phospho-STAT3 levels, which is a key intracellular mediator of IL-6 signalling (p < 0.05). Furthermore, treatment with anti-IL-6 neutralizing antibody blocked the effects of PE serum on neurite growth (p < 0.05), and exposure to IL-6 promoted neurite growth in SH-SY5Y cells (p < 0.01). Discussion: Collectively these data show elevated serum levels of maternal IL-6 in PE, which increases neurite growth and mitochondrial function in SH-SY5Y cells. This rationalizes the further study of IL-6 as a potential mediator between PE exposure and neurodevelopmental outcome in the offspring.

Aminothiols exchange in coronavirus disease 2019

Abstract Objective Clinical manifestation of the inflammatory process in its relation to biochemical markers (total cysteine [Cys], cysteine-glycine [CysGly], glutathione [GSH], glutamate-cysteine [Glu-Cys], homocysteine [Hcy], the ratio of reduced to oxidized glutathione [GSH/GSSG], the ratio of reduced to oxidized cysteine [CySH/CySS], malondialdehyde-oxidized low-density lipoproteins [MDA-oxLDL]) has been studied in patients with coronavirus disease 2019 (COVID-19). Material and methods 48 patients with mild to severe COVID-19 and 20 healthy volunteers were included in our research. The participants were divided into 4 experimental groups according to inflammation intensity estimated based on the serum levels of interleukin 6 (IL-6). Results All 4 groups showed the prevalence of male patients and elevated serum levels of IL-6 (by 54.6%). There was no comorbidity in patients with mild COVID-19 (nasopharyngitis symptoms) and in healthy control subjects. 50% of patients with lung damage had accompanying diseases. Alterations of aminoethyl metabolism were detected in COVID-19 patients: as reflected by the decreased levels of Cys, CysGly, and Glu-Cys and the increased levels of GSH as compared to the control group. Conclusion Elevation of IL-6 over 7.5 pg/mL was associated with decreased GSH/GSSG and CySH/CySS ratios indicating enhanced oxidative stress and was followed by protein oxidation, specifically MDA-oxLDL.

A serum interleukin-6-based analysis of patients with nasopharyngeal swab reverse-transcriptase polymerase chain reaction negative for SARS-COV-2 infection with CO-RADS 4 and 5 on computed tomography of the chest

Background: Serum interleukin 6 (IL-6) levels have been studied in the diagnostic evaluation of patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) disease (COVID-19).Methods: We studied the utility of treatment with tocilizumab in COVID-19 patients (n=19) with a negative nasopharyngeal swab real time reverse transcriptase polymerase chain reaction (RT-PCR) test for SARS-CoV-2 who had suggestive computed tomography (CT) findings, namely, COVID-19 Reporting and Data System (CO-RADS) 4,5.Results: Receiver operator characteristic (ROC) curve analysis showed that serum IL 6 at a cut-off of >56.9 pg/L was a predictor of mortality in nasopharyngeal swab RT-PCR negative patients with suggestive CT findings. Tocilizumab had no significant effect on the mortality.Conclusions: In nasopharyngeal swab RT-PCR negative patients with suggestive chest CT findings, elevated serum IL-6 levels > 56.9 pg/L predicted mortality. However, treatment with tocilizumab had no effect on mortality.

Migraine chronification is associated with higher body mass index and elevated serum interleukin-6 levels

Background/Aim: Chronification of migraine is a serious health problem with difficulties in management and related to increased disability. Inflammation is suggested to have a role in migraine and its chronification. We aimed to determine whether systemic inflammatory response tested by serum interleukin-6 (IL-6) levels and obesity were related to migraine attack frequency. Methods: A total of 40 female participants (20 chronic migraine, 10 episodic migraine, 10 healthy controls without headache) were included in the study. None of the migraine patients were on migraine prophylaxis. Episodic migraine patients were evaluated interictally with a 72 hour headache free period before and after blood collection. Migraine headache frequency, body mass index (BMI) and age of the patients were recorded. Serum IL-6 levels were measured by ELISA method. Results: Serum IL-6 levels were significantly elevated in chronic migraine patients compared to episodic migraine patients and healthy controls. BMI was higher in chronic migraine patients compared to episodic migraine patients and healthy subjects even though it did not reach statistical significance. Serum IL-6 levels and BMI were positively correlated with migraine headache frequency. Conclusion: Elevated systemic circulating IL-6 levels and BMI were related to an increase in migraine headache frequency. BMI and serum IL-6 levels seem to be risk factors for chronic migraine in women. Strategies to reduce inflammation and obesity must be integrated to the treatment of chronic migraine. Identification of modifiable risk factors for chronification of migraine is crucial for sustainable treatment of migraine.

The Role of IL-18 and Human Cytomegalovirus in Type 1 Diabetes Mellitus in Thi-Qar Province

Previous studies indicated that elevated serum levels of Interleukin -18 (IL-18) and human cytomegalovirus (HCMV) antibodies have a fundamental role in the pathogenesis of Type I diabetic mellitus T1DM. Therefore, the aim of the current study was to investigate the possible overlap between human cytomegalovirus (HCMV) and Interleukin-18 (IL-18) with the pathogenesis of T1DM. The serum of (45) T1DM patients and (45) healthy controls were used to detect IL-18 levels with an ELISA Kit and detect HCMV with cobas c411 apparatus for detect IgM and IgG HCMV.&#x0D; The results showed that the levels of IL-18 and human CMV IgM, IgG were significantly higher in patients with type 1 diabetes compared to the control group (45.8773 ±12.196 and 0.52 ± 0.25, 63.52 ±13.0 pg/ml for patients respectively) versus (12.611 ±3.9 and 0.11 ±0.01, 0.261 ±0.68 pg/ml for healthy subjects, respectively); The values were ​​at P value ≤ 0.05.&#x0D; The results of the data concluded that there was a significant increase of IL-18 and human CMV IgM, IgG in the serum of the patient group compared to the lower levels in the control group, indicating that these markers may be involved in the pathogenesis and development of T.&#x0D; These data concluded that there was a significant increase in serum IL-18 and HCMV Abs, compared to the lower levels in the control group, indicating that these markers may be involved in the pathogenesis and development of T1DM.

Promising Neutrophil-Associated Biomarkers in Lung Diseases of Patients with Antisynthetase Syndrome and Dermatomyositis.

Objectives Antisynthetase syndrome (ASS) and dermatomyositis (DM) are serious autoimmune diseases, with lungs being the most frequently involved organ and sometimes fatal. This study is aimed at clarifying the role of neutrophil-associated biological markers in suggesting ASS and DM-associated respiratory infections and interstitial lung diseases. Methods We carried out a retrospective review of the medical records of 46 cases of ASS and DM diagnosed at the Second Hospital of Zhejiang University College of Medicine, between January 2017 and December 2020. Serum myeloperoxidase (MPO), neutrophil elastase (NE), α1 anti-trypsin (AAT), and interleukin-6 (IL-6) were also detected. Results Gottron's sign is characteristic of dermatomyositis, while polyarthritis is more characteristic of ASS. Pulmonary function is worse in ASS than in DM patients. Patients with ASS and DM had abnormal lymphocyte and neutrophil counts compared to healthy subjects, but not in relation to lung function and rapid progression of interstitial lung disease (RP-ILD). Elevated serum NE, MPO, and IL-6 levels are suggestive of respiratory infections, whereas decreased circulating IL-6 is predictive of RP-ILD. Conclusion Our study identified the neutrophil-associated biomarkers MPO, NE, and IL-6 as promising indicators with different suggestive roles in respiratory infections and interstitial lung diseases in patients with ASS and DM.

Gabexate Mesylate-Poloxamer 407 Conjugate Alleviates Sodium Taurocholate-Induced Severe Acute Pancreatitis in an Optimized Rat Model.

We have previously shown that gabexate mesylate-poloxamer 407 conjugate (GMTI) alleviates traumatic pancreatitis in rats. In this study, we evaluated the therapeutic effect of GMTI on sodium taurocholate-induced severe acute pancreatitis (SAP) in an optimized rat model. An SAP rat model was established via microinjection of 3.5% sodium taurocholate and retention in the bile duct for 1min. SAP rats were administered GMTI via tail vein injection (i.v.) or tail vein injection + intraperitoneal injection (i.v. + i.p.). All rats were sacrificed at 12h after treatment. Biochemical approach and enzyme-linked immunosorbent assay were performed to measure the serum levels of amylase (AMY), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6). Hematoxylin and eosin staining and TUNEL assay were conducted to examine histopathology and acinar cell apoptosis in the rat pancreas. SAP was successfully induced in all model rats, as evidenced by progressively aggravating SAP symptoms and signs, pancreatic histopathological abnormalities, as well as elevated serum levels of TNF-α, IL-6, and AMY. The mortality rates at 1h, 6h, and 12h were 0%, 0%, and 25%, respectively. GMTI therapy via i.v. or i.v. + i.p. significantly reduced pancreatic wet weights, ascites amounts, pathological scores, and circulating levels of TNF-α and IL-6 while promoting acinar cell apoptosis in SAP rats. GMTI therapy via i.v. + i.p. outperformed i.v. in improving pancreatic histology and reducing TNF-α and IL-6 serum levels in SAP rats. Our optimized SAP rat model is reliable and reproducible. GMTI therapy is a promising approach against SAP.

Inflammatory Blood Biomarker Kynurenine Is Linked With Elevated Neuroinflammation and Neurodegeneration in Older Adults: Evidence From Two 1H-MRS Post-Processing Analysis Methods.

Rationale and ObjectivesPro-inflammatory processes have been argued to play a role in conditions associated with cognitive decline and neurodegeneration, like aging and obesity. Only a limited number of studies have tried to measure both peripheral and central biomarkers of inflammation and examined their interrelationship. The primary aim of this study was to examine the hypothesis that chronic peripheral inflammation would be associated with neurometabolic changes that indicate neuroinflammation (the combined elevation of myoinositol and choline), brain gray matter volume decrease, and lower cognitive functioning in older adults.Materials and MethodsSeventy-four older adults underwent bio-impedance body composition analysis, cognitive testing with the Montreal Cognitive Assessment (MoCA), blood serum analysis of inflammatory markers interleukin-6 (IL-6) and kynurenine, magnetic resonance imaging (MRI), and proton magnetic resonance spectroscopy (1H-MRS) of the brain. Neurometabolic findings from both Tarquin and LCModel 1H-MRS post-processing software packages were compared. The regions of interest for MRI and 1H-MRS measurements were dorsal posterior cingulate cortex (DPCC), left hippocampal cortex (HPC), left medial temporal cortex (MTC), left primary sensorimotor cortex (SM1), and right dorsolateral prefrontal cortex (DLPFC).ResultsElevated serum kynurenine levels were associated with signs of neuroinflammation, specifically in the DPCC, left SM1 and right DLPFC, and signs of neurodegeneration, specifically in the left HPC, left MTC and left SM1, after adjusting for age, sex and fat percentage (fat%). Elevated serum IL-6 levels were associated with increased Glx levels in left HPC, left MTC, and right DLPFC, after processing the 1H-MRS data with Tarquin. Overall, the agreement between Tarquin and LCModel results was moderate-to-strong for tNAA, tCho, mIns, and tCr, but weak to very weak for Glx. Peripheral inflammatory markers (IL-6 and kynurenine) were not associated with older age, higher fat%, decreased brain gray matter volume loss or decreased cognitive functioning within a cohort of older adults.ConclusionOur results suggest that serum kynurenine may be used as a peripheral inflammatory marker that is associated with neuroinflammation and neurodegeneration, although not linked to cognition. Future studies should consider longitudinal analysis to assess the causal inferences between chronic peripheral and neuroinflammation, brain structural and neurometabolic changes, and cognitive decline in aging.

Elevated serum levels of interleukin -22 and interleukin-23 in pediatric asthma

Background: There are few studies had addressed the association between serum levels of Interleukin -22 and Interleukin-23 with severity of asthma, this study aims to evaluate whether elevated IL-22 and IL-23 serum levels is related to the severity of asthma. Methods: This study is a case-control study that included 60 asthmatic children (35 male and 25 female) as the patients group age ranged between 4 months to 14 years old, and 60 non-asthmatic (32 male and 28 female) age-matched patients group attending the outpatient clinic were recruited as control group. Serum levels of IL-22 and IL-23 was measured by sandwich ELISA using ELISA kits. Results: The results of this study have shown an elevated serum level of IL-23 in patients group compared with control group with significant (p= 0.008) and there was no significant difference between patients and control regarding IL-22 serum level (p = 0.721) in asthmatic children. Conclusion: According to the current study the serum level of IL-23 showing a significant association with the asthma severity in children.

Metabotropic glutamate receptor 5 blockade attenuates pathological cardiac remodelling in pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is characterized by cardiac remodelling. Glutaminolysis plays a crucial role in PAH-induced remodelling. The metabotropic glutamate receptor 5(mGluR5) may mediate this process. This study investigated whether or not the blockade of mGluR5may attenuate PAH-induced pathological cardiac remodelling. Pulmonary arterial hypertension was induced by intraperitoneally injecting male Sprague-Dawley (SD) rats with 60mg/kg of monocrotaline (MCT). 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine (MTEP) (10 mg/kg intraperitoneally) was used as a therapeutic intervention to block mGluR5. Cardiac functions were assessed with right heart catheterization and electrocardiography. Alterations in protein expressions and inflammatory markers were investigated using western blot and enzyme-linked immunosorbent assay (ELISA), respectively. Increased right ventricular systolic pressure (RSVP), elevated protein expressions of mGluR5, collagen types I and III and cartilage intermediate layer protein 1 (CILP1), enhanced phosphorylation of phosphatidylinositol 3-kinase (PI3K), AKT and p38 mitogen-activated protein kinase (P38MAPK), increased angiopoietin 2 (Ang 2) and vascular endothelial growth factor-α (VEGF) protein expressions and elevated serum levels of interleukin 6 (IL-6) and tumour necrotic factor α (TNF-α) were observed in MCT-induced PAH rats. MTEP improved hemodynamics and right ventricular hypertrophy. MTEP also attenuated MCT-induced elevations in the protein expressions of mGluR5, collagen types I and III, CILP1, Ang 2 and VEGF and decreased PI3K, AKT and P38MAPK phosphorylations and inflammatory cytokine levels. Metabotropic glutamate receptor 5 blockade using MTEP ameliorates PAH-induced pathological right cardiac remodelling via inhibiting the signalling cascade involving PI3K/AKT, P38MAPK, Ang 2 and VEGF.

Association of Interleukin-6 Levels with Morbidity and Mortality in Patients with Coronavirus Disease 2019 (COVID-19).

The prognostic value of interleukin-6 (IL-6) in coronavirus disease 2019 (COVID-19) needs to be clarified. In this retrospective study, COVID-19 patients treated at Renmin Hospital of Wuhan University from January 7 to February 8, 2020 with measurements of serum IL-6 levels within 1 week after admission were included. Data regarding demographics, clinical characteristics, laboratory tests, complications, and outcomes were collected and analyzed. Sixty-six patients diagnosed with COVID-19 were included in this study (31 patients were females). They were divided into a normal group (serum IL-6 <10 pg/mL, n = 35) and an abnormal group (serum IL-6 <10 pg/mL, n = 31). Compared with the normal group, the incidence of critical cases (P <0.001), acute respiratory distress syndrome (ARDS) (P = 0.001), acute cardiac injury (P = 0.002), cardiac insufficiency (P = 0.039), mechanical ventilation rate (P = 0.002), and mortality (P = 0.021) was significantly increased in the abnormal group. Serum IL-6 concentration was an independent predictor of fatal outcome (P = 0.04). The optimal cutoff value of serum IL-6 concentration for predicting fatal outcomes was 26.09 pg/mL (P <0.001). In COVID-19, elevated serum IL-6 levels were associated with critical illness, use of mechanical ventilation, and complications, including heart injury and ARDS, and could predict a fatal outcome. Early detection of serum IL-6 levels after admission should be necessary in COVID-19 patients.

Perioperative management of a patient undergoing resection of interleukin-6 producing pheochromocytoma

BackgroundPheochromocytomas produce hormones, cytokines, and catecholamines. We report perioperative anesthetic management of a rare interleukin-6 (IL-6)-producing pheochromocytoma.Case presentationA 32-year-old female was scheduled for laparoscopic adrenalectomy for pheochromocytoma. She had a sustained high fever with elevated serum noradrenaline and IL-6 levels. The persistent high inflammatory state, followed by anemia, malnutrition, and coagulopathy, led us to prepone her date of surgery. During general anesthesia, alpha-blockers allowed hemodynamic fluctuations to be controlled. During surgery, simultaneous increases in noradrenaline and IL-6 levels were observed, which rapidly declined after tumor removal. Her postoperative course was uneventful, without pulmonary edema caused by cytokine storms.ConclusionsThe conventional pheochromocytoma strategy allowed surgical removal of an IL-6-producing pheochromocytoma under general anesthesia. However, management of high inflammatory states that induce anemia and coagulopathy is necessary.

Correlation of Serum IL-6 Levels with Muscle Mass, Muscle Strength, and Physical Performance in Elderly Gymnastics Community in Mohammad Hoesin General Hospital Palembang

Introduction. Old age is related to geriatric syndrome where there are several health problems that often occur related to a decrease in body function and an increase in the inflammatory process. Decrease in muscle mass, muscle strength and physical performance will cause a condition of sarcopenia and frailty syndrome in the elderly. The importance of prevention so that sarcopenia does not occur in the elderly by evaluating the factors that can cause it, one of which is controlling interleukin 6 (IL-6) as proinflammatory. The purpose of this study was to determine the correlation between serum IL-6 levels with muscle mass, muscle strength and physical performance in the elderly gymnastics-community in Mohammad Hoesin General Hospital, Palembang.&#x0D; Methods. This research is an observational analytic study with a cross-sectional approach which was conducted at the Integrated Geriatric Clinic Internal Medicine RSMH Palembang from November 2019 to November 2020. A sample of 31 people aged &gt; 60 years was examined for muscle mass, muscle strength, physical performance and IL-levels. 6 serum. All data processing and analysis in this study used the SPSS version 25 for Windows program.&#x0D; Results. of the 31 subjects, 27 were female (87.1%) and 4 male (12.9%). The mean value of muscle mass is37.9 kg/m2, muscle strength 23 kg, and physical performance 6.1 m/sec.There were 28 (90.3%) samples with elevated serum IL-6 levels, while 3 (9.7%) samples had normal levels. There was a significant negative correlation (p = 0.000) with a strong correlation strength (r = -0.722) between serum IL-6 levels and muscle mass and a significant negative correlation (p = 0.050) with a weak correlation strength (r = -0.354) between IL levels -6 serums with physical performance.&#x0D; Conclusions. There was a significant negative correlation between serum IL-6 levels and muscle mass and physical performance. So, it is very important to prevent an increase in serum IL-6 levels so that the elderly do not fall into a state of sarcopenia.