Higher Serum Levels Of IL-6 Research Articles

Immune reconstitution and evolution of B-cell–stimulating cytokines after R-CHOP therapy for HIV-associated DLBCL

AbstractHIV infection is associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) that persists despite the advent of combined antiretroviral therapy. In this prospective study, we analyzed the evolution of B-cell activating cytokines (interleukin-6 [IL-6], IL-10, and B-cell activating factor [BAFF]) and the coevolution of main functional subsets of circulating B and T cells in 51 patients with HIV-associated DLBCL treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, Oncovin [vincristine], and prednisone). R-CHOP therapy was associated with a decrease of IL-10, whereas IL-6 levels fluctuated, and BAFF levels increased during the first 3 months and decreased thereafter. We observed a rapid rise in CD19+ B cells composed mostly of naïve B cells whereas marginal zone–like B cells and memory B cells recovered gradually. With a median follow-up of 41 months, progression-free survival and overall survival at 5 years were 61.8% (95% confidence interval [CI], 47.6-80.4) and 67.4% (95% CI, 53.4-85.0), respectively. Progression (17.5%) and sepsis (12.5%) were the main causes of death. Baseline risk factors for death and progression were poor revised International Prognostic Index (P = .049), natural killer cell lymphopenia (P = .001), lower proportion of naïve B cells among B-cell compartment (P = .017), and higher IL-6 serum levels (P = .001). Our data suggest that patients treated with R-CHOP for HIV-associated DLBCL have a disturbed peripheral B-cell compartment and that the low pool size of circulating naïve B cells negatively affects clinical outcome in these patients. In an era of rapid development of B-cell–depleting therapies including B-cell–targeting chimeric antigen receptor T cells, baseline and posttreatment assessment of perturbations within nontumoral B-cell counterparts are warranted for proper risk profiling in HIV-associated DLBCL. This trial was registered at www.ClinicalTrials.gov as #NCT01164436.

The potential role of interleukin-6 in the association between inflammation and cognitive performance in obstructive sleep apnea

BackgroundInterleukin-6 (IL-6) represents one of the main molecules involved in inflammatory responses, which can be altered in either patients with cognitive impairment or obstructive sleep apnea (OSA). The present study aimed to evaluate serum IL-6 levels and cognitive performance in patients with severe OSA (Apnea-Hypopnea Index - AHI >30/h). MethodsThirty patients with severe OSA were compared to 15 controls similar in age, sex, and Body Mass Index. All patients underwent a sleep medicine interview, including the Epworth Sleepiness Scale (ESS), a polygraphic cardiorespiratory recording, the Montreal Cognitive Assessment (MoCA), and a blood sample for serum IL-6 assessment. ResultsOSA patients presented higher IL-6 serum levels (Md = 7.38) than controls (Md = 2.20, p < 0.001). Moreover, OSA patients showed lower MoCA (Md = 27.00) and higher ESS scores (Md = 8.00) than controls (Md = 30.00, p < 0.001; Md = 4.00, p = 0.004, respectively). Higher IL-6 serum levels were associated with lower oxygen saturation parameters and MoCA scores. ConclusionsThis study documented an association between inflammation, featured by higher IL-6 serum levels, and both nocturnal hypoxemia and cognitive impairment in OSA patients. Therefore, the increase in IL-6 levels may represent the result of vascular damage and neuroinflammation due to intermittent nocturnal hypoxia and further causing neurocognitive dysfunction in OSA.

Long-term efficacy of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in two patients with sJIA and recurrent episodes of MAS.

Systemic juvenile idiopathic arthritis (sJIA), a multifaceted autoinflammatory disorder, can be complicated by life-threatening conditions such as macrophage activation syndrome (MAS) and interstitial lung disease (ILD). The management of these conditions presents a therapeutic challenge, underscoring the need for innovative treatment approaches. to report the possible role of MAS825, a bispecific anti-IL1β and IL-18 monoclonal antibody, in the treatment of multi-drug-resistant sJIA. We report two patients affected by sJIA with severe and refractory MAS and high serum IL-18 levels, responding to dual blockade of IL-1β and IL-18. The first patient is a 20-year-old man, presenting a severe MAS complicated by thrombotic microangiopathy, following SARS-CoV-2 infection. He was treated with MAS825, with quick improvement. Eighteen months later, the patient is still undergoing biweekly treatment with MAS825, associated with MTX, ciclosporin and low-dose glucocorticoids, maintaining good control over the systemic features of the disease.The second patient, a 10-year-old girl, presented a severe MAS case, complicated by posterior reversible encephalopathy syndrome (PRES), following an otomastoiditis. The MAS was not fully controlled despite treatment with IV high-dose glucocorticoids, anakinra and ciclosporin. She began biweekly MAS825, which led to a prompt amelioration of MAS parameters. After 10 months, the patient continues to receive MAS825 and is in complete remission. In light of the pivotal role of IL-1β and IL-18 in sJIA, MAS and ILD, MAS825 might represent a possible valid and safe option in the treatment of drug-resistant sJIA, especially in the presence of high serum IL-18 levels.

IL-6 and TIMP-1 Correlated to Airway Pathogen Colonization and Predict Disease Severity in Patients with Non-Cystic Fibrosis Bronchiectasis.

Non-cystic fibrosis bronchiectasis is associated with airway pathogen colonization. We planned to investigate the inflammatory markers in patients with different airway pathogens and their correlation with disease severity. We enrolled patients aged between 20 and 75 from October 2021 to August 2022. All patients had sputum evaluation for bacterial and fungal cultures before enrollment, and were classified into four groups according to the culture results. Forty-four patients with non-CF bronchiectasis and six controls were enrolled and categorized as follows: Group 1, no pathogens identified in sputum cultures (n = 14); Group 2, positive fungal culture results (n = 18); Group 3, positive P. aeruginosa culture results (n = 7); and Group 4, positive culture results for both fungi and P. aeruginosa (n = 5). Group 4 had significantly higher serum defensin α1, IL-6 and tissue inhibitors of MMP (TIMP)-1 levels than group 1 patients. The serum levels of IL-6 and TIMP-1 were positively correlated with the FACED score and negatively correlated with distance-saturation product. Significantly higher levels of serum IL-6 and TIMP-1 were found in the patients who had concomitant fungal and P. aeruginosa colonization, and were closely related to clinical severity and may have important roles in disease monitoring.

Peripheral Blood Mononuclear Cells and Serum Cytokines in Patients with Lupus Nephritis after COVID-19.

Systemic lupus erythematosus (SLE) patients have an increased risk of infections and infection-related mortality. Therefore, during the global SARS-CoV-2 pandemic, SLE patients were particularly vulnerable to SARS-CoV-2 infections. Also, compared to other patients, SLE patients seem to develop more severe manifestations of coronavirus disease 2019 (COVID-19), with higher rates of hospitalization, invasive ventilation requirements, or death. This study evaluated the immune parameters after SARS-CoV-2 infection in SLE patients. We analyzed subpopulations of peripheral blood cells collected from patients with renal manifestation of SLE (lupus nephritis, LN). LN patients were divided into two subgroups: those unexposed to SARS-CoV-2 (LN CoV-2(-)) and those who had confirmed COVID-19 (LN-CoV-2(+)) six months earlier. We analyzed basic subpopulations of T cells, B cells, monocytes, dendritic cells (DCs), and serum cytokines using flow cytometry. All collected data were compared to a healthy control group without SARS-CoV-2 infection in medical history. LN patients were characterized by a decreased percentage of helper T (Th) cells and an increased percentage of cytotoxic T (Tc) cells regardless of SARS-CoV-2 infection. LN CoV-2(+) patients had a higher percentage of regulatory T cells (Tregs) and plasmablasts (PBs) and a lower percentage of non-switched memory (NSM) B cells compared to LN CoV-2(-) patients or healthy controls (HC CoV-2(-)). LN patients had a higher percentage of total monocytes compared with HC CoV-2(-). LN CoV-2(+) patients had a higher percentage of classical and intermediate monocytes than LN CoV-2(-) patients and HC CoV-2(-). LN CoV-2(+) patients had higher serum IL-6 levels than HC CoV-2(-), while LN CoV-2(-) patients had higher levels of serum IL-10. LN patients are characterized by disturbances in the blood's basic immunological parameters. However, SARS-CoV-2 infection influences B-cell and monocyte compartments.

The associations of peripheral interleukin alterations and hippocampal subfield volume deficits in schizophrenia.

The hippocampus is one of the brain regions most vulnerable to inflammatory insults, and the relationships between peripheral inflammation and hippocampal subfields in patients with schizophrenia remain unclear. In this study, forty-six stably medicated patients with schizophrenia and 48 demographically matched healthy controls (HCs) were recruited. The serum levels of IL - 1β, IL-6, IL-10, and IL-12p70 were measured, and 3D high-resolution T1-weighted magnetic resonance imaging was performed. The IL levels and hippocampal subfield volumes were both compared between patients and HCs. The associations of altered IL levels with hippocampal subfield volumes were assessed in patients. Patients with schizophrenia demonstrated higher serum levels of IL-6 and IL-10 but lower levels of IL-12p70 than HCs. In patients, the levels of IL-6 were positively correlated with the volumes of the left granule cell layer of the dentate gyrus (GCL) and cornu Ammonis (CA) 4, while the levels of IL-10 were negatively correlated with the volumes of those subfields. IL-6 and IL-10 might have antagonistic roles in atrophy of the left GCL and CA4. This suggests a complexity of peripheral cytokine dysregulation and the potential for its selective effects on hippocampal substructures, which might be related to the pathophysiology of schizophrenia.

Evaluation of cytokine expressions in patients with recurrent aphthous stomatitis: A systematic review and meta-analysis.

This systematic review and meta-analysis aimed to evaluate the expression levels of various T helper (Th) cell-secreted cytokines in recurrent aphthous stomatitis (RAS). Case-control studies comparing the serum or salivary levels of cytokines between RAS patients and healthy controls were searched in PubMed, EMBASE, Web of Science, and Google Scholar prior to September 30, 2023. Cytokines produced by Th1 (interleukin [IL]-1, IL-2, IL-8, IL-12, tumor necrosis factor alpha [TNF-α], interferon gamma [IFN-γ]), Th2 (IL-4, IL-5, IL-6, IL-10, IL-13), and Th17 (IL-17A) cells were investigated. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated to detect the difference. A total of 20 studies comprising 1070 RAS patients and 536 healthy controls were included. RAS patients had significantly higher salivary levels of IL-2 (SMD = 4.15, 95%CI 0.83-7.48), IL-5 (SMD = 0.53, 95%CI 0.05-1.00), IL-6 (SMD = 0.48, 95%CI 0.12-0.84), IL-12 (SMD = 0.94, 95%CI 0.18-1.71), and TNF-α (SMD = 1.31, 95%CI 0.44-2.18) compared to healthy controls. Serum levels of IL-6 (SMD = 0.48, 95%CI 0.30-0.66), TNF-α (SMD = 0.70, 95%CI 0.22-1.17), and IFN-γ (SMD = 0.72, 95%CI 0.17-1.28) were significantly increased, while serum IL-10 levels (SMD = -2.25, 95%CI -3.99 to -0.52) were reduced in RAS patients. Patients diagnosed with major RAS had markedly elevated serum IL-8 levels (SMD = 0.39, 95%CI 0.07-0.71) and a trend toward higher serum IL-6 levels (SMD = 0.51, 95%CI -0.02 to 1.04) than those with minor RAS. In conclusion, Th1/Th2-related cytokines, especially IL-2, IL-6, and TNF-α, are involved in the pathogenesis of RAS development and progression and are potential therapeutic targets for RAS.

Search in the Periphery for Potential Inflammatory Biomarkers of Dementia with Lewy Bodies and Alzheimer's Disease.

Neuroinflammation, with altered peripheral proinflammatory cytokine production, plays a major role in the pathogenesis of neurodegenerative diseases, such as Alzheimer's disease (AD), while the role of inflammation in dementia with Lewy bodies (DLB) is less known and the results of different studies are often in disagreement. The present study aimed to investigate the levels of TNFα and IL-6 in serum and supernatants, and the related DNA methylation in patients affected by DLB and AD compared to healthy controls (HCs), to clarify the role of epigenetic mechanisms of DNA promoter methylation on of pro-inflammatory cytokines overproduction. Twenty-one patients with DLB and fourteen with AD were frequency-matched for age and sex with eleven HCs. Clinical evaluation, TNFα and IL-6 gene methylation status, cytokine gene expression levels and production in serum and peripheral blood mononuclear cell (PBMC) supernatants were performed. In AD and DLB patients, higher serum levels of IL-6 and TNFα were detected than in HCs. Differences in LPS-stimulated versus spontaneous PBMCs were observed between DLB, AD, and HC in the levels of TNFα (p = 0.027) and IL-6 (p < 0.001). Higher levels were also revealed for sIL-6R in DLB (p < 0.001) and AD (p < 0.001) in comparison with HC.DNA hypomethylation in IL-6 and TNFα CpG promoter sites was detected for DLB and AD patients compared to the corresponding site in HCs. Our preliminary study documented increased levels of IL-6 and TNFα in DLB and AD patients to HCs. This overproduction can be due to epigenetic mechanisms regarding the hypomethylation of DNA promoters.

#71 Dysregulation of ITGAM and ITGB2 in the pathogenesis of diabetic kidney disease—results from bioinformatics analysis and in vitro studies

Abstract Background and Aims Activated neutrophils can release web-like chromatin structures known as neutrophil extracellular traps (NETs), but their roles in the immunopathogenesis of diabetic kidney disease (DKD) remains elusive. Method The characteristic NETs associated targets of differentially expressed genes (DEGs) from human kidney biopsy datasets of patients with DKD (GSE30528 and GSE30529) were identified by machine learning method (LASSO and SVM-RFE). The genes expression was further validated using kidney biopsy dataset of GSE142025. The most abundant single cell of the targets in DKD was further selected by single-nucleus RNA sequencing datasets (GSE131882). Predictive pathway network of targeted genes was constructed using GENEMANIA database. The expressions and potential signaling pathway of these candidate genes were validated using flow cytometry and ELISA. Results Three predicting NETs related genes (ITGAM, ITGB2 and TLR7), identified by machine learning algorithms, which all showed significant upregulation in both glomerular and tubulointerstitial compartments in human DKD kidney samples. Single-cell analysis suggested that ITGAM, ITGB2 and TLR7 were most enriched in leucocytes. DKD patients (n = 18) showed significantly higher activated neutrophils as well as increased expression of ITGAM and ITGB2 compared to healthy controls (HCs, n = 9). DKD patients also exhibited higher serum levels of IL6 but lower IL-10 than HCs (all p &amp;lt; 0.01). The significant network of IL10, IL6, ITGAM and ITGB2 was generated. This network might be associated with leukocyte activation, macrophage activation, JAK-STAT pathway, acute inflammatory response and lymphocyte immune response (all p &amp;lt; 0.05). Conclusion Aberrant ITGAM and ITGB2 expressions in activated neutrophils contribute to DKD pathogenesis and may serve as novel therapeutic targets for DKD.

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.

Association of high disease activity and serum IL-6 levels with the incidence of inflammatory major organ events in Behçet disease: a prospective registry study.

Little is known about the relationship between the disease activity of Behçet disease (BD) and the incidence of inflammatory major organ events. In this prospective registry study, we investigated the association between the Behçet Disease Current Activity Form (BDCAF) and incidence of inflammatory major organ events, defined as the inflammation of the ocular, central nervous, intestinal, and vascular systems in BD. We enrolled participants from Japanese multicenter prospective cohorts. The BDCAF was evaluated annually. BD-related symptoms, including inflammatory major organ events, were monitored. The association between BDCAF and inflammatory major organ events was analyzed by time-to-event analysis. An unsupervised clustering of the participants' BDCAF, therapeutic agents, and multiple serum cytokines was also performed to examine their association with inflammatory major organ events. A total of 260 patients were included. The patients had a median BDCAF score of 2 [Interquartile range, 1-3] at the enrolment and remained disease active at 1- and 2-year follow-ups, indicating residual disease activity in BD. Patients with a BDCAF score of 0 had a longer inflammatory major organ event-free survival at 52 weeks than those with a score of 1 or higher (p=2.2 x 10-4). Clustering analysis revealed that patients who did not achieve remission despite treatment with tumor necrosis factor inhibitors had high serum inflammatory cytokine levels and incidences of inflammatory major organ events. Among the elevated cytokines, IL-6 was associated with inflammatory major organ events. This study suggests that treatment strategies targeting overall disease activity and monitoring residual serum IL-6 may help prevent inflammatory major organ events in BD.

Abstract 627: IL-6 signaling via JAK/STAT axis influences PIM1 expression in renal cell carcinoma

Abstract Renal cell carcinoma (RCC) is a top ten malignancy in the U.S. Overexpression of the proviral integration site for moloney murine leukemia virus 1 (PIM1) kinase is associated with poor clinical outcomes in RCC patients. PIM1 is a constitutively active serine/threonine kinase promoting cell proliferation, apoptosis resistance, invasion, and migration. The mechanisms underlying PIM1 expression and its function in RCC are not fully delineated. IL-6 is a pleiotropic cytokine that activates the JAK/STAT signaling cascade. High serum IL-6 levels are associated with the poor prognosis of RCC patients and may contribute to RCC invasion and metastasis. STAT3/5 binds directly to the PIM1 promoter inducing PIM1 expression. An IL-6/STAT3/PIM1 axis exists in pancreatic and breast cancer. We previously reported that PIM1 is overexpressed in a panel of human RCC cell lines relative to normal and immortalized renal proximal tubule epithelial cells. We also identified that RCC cells secrete IL-6. Our prior studies suggest that differential expression of PIM1 may be linked to autocrine IL-6 signaling. We thus hypothesize that an IL-6/JAK/STAT pathway regulates the expression of PIM1 in RCC. To understand how IL-6 signaling through the JAK/STAT pathway may regulate PIM1 expression in RCC cells, we examined whether IL-6 blockade using anti-IL-6 antibody or tocilizumab, would modulate PIM1 expression. Similarly, we assessed whether ruxolitinib, and LLL12, a STAT3 inhibitor could regulate PIM1 expression. We then evaluated the effect of ruxolitinib treatment on cell viability. In RCC cell lines, IL-6 blockade through either anti-IL-6 antibody or tocilizumab was sufficient to decrease PIM1 protein levels. Treatment with ruxolitinib leads to a dose and time-dependent decrease in PIM1 levels. Incubation with a STAT3 inhibitor also resulted in decreased PIM1 levels in RCC cells. Treatment with ruxolitinib also appears to decrease cell viability in a dose-dependent manner. These results suggest that differential expression of PIM1 in RCC may be linked to autocrine IL-6 signaling via a JAK/STAT/PIM1 axis. Multiple FDA-approved agents are available that target this pathway. Further investigation is required to determine the efficacy of these agents in pre-clinical models and even clinical trials. Citation Format: Kimberly S. Meza, Kimberly Seymour, Sheldon L. Holder. IL-6 signaling via JAK/STAT axis influences PIM1 expression in renal cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 627.

Abstract B025: IL6 signaling in pre-malignant obese endometrium and endometrial cancer

Abstract Objective: Obesity associated chronic inflammatory status plays a role in the increased endometrial cancer incidences, IL-6 is one of those inflammatory molecules. To explore the potential of targeting pro-inflammation factors for endometrial cancer prevention, using multi-platform and multi-model analysis, we investigated IL6 and its associated signaling in pre-malignant endometrium and low-grade endometrial cancer. Methods: Illumina microarray and Nanostring nCounter® Pancancer Immune profiling panel gene expression profiling was performed on pre-malignant obese endometrium from diet induced obese Wistar rats, and endometrium from obese patients, lean endometrium was used as control. Clariom D assay was performed on RNA extracted from the gland and stroma of human obese endometrial carcinoma (OEC) and obese normal endometrium (ONE). IPA, nSolver, Transcriptome Analysis Console (TAC), and CIBERSORTx were used for data analysis. Ishikawa cells were 2D and 3D cultured, or 3D co-cultured with endometrial stroma cell line SHT290. Western blot was used for testing cell signal activity. Results: Pronounced IL-6 signaling (Z-score:2.3333, p=2.48E-02) was shown in pre-malignant obese endometrium of diet induced obese rats compared with lean littermates: NF-kB signaling (Z-score:2.714, p=3.47E-02), STAT3 signaling (Z-score:2.53, p=6.56E-04), and tumor microenvironment pathway (Z-score: 3.441, p=6.81E-05) were enhanced; PTEN signaling (Z-score:-1.997, p=2.76E-03) was attenuated. IL6R (FC=1.64, p=0.017), MMP2 (FC=1.938, p=0.026), IL1R2 (FC=1.75, p&amp;lt;0.0001), and CCL2 (FC=2.251, p=0.002) expression were increased. IL6 induced stronger STAT3 signaling, and weaker activation of MAPK signaling in Ishikawa cells 3D co-cultured with stroma cells, compared with 3D cultured Ishikawa cells without stroma cells. No IL-6 induced activation of MAPK signaling was observed with activation of Stat3 signaling in 2D-cultured Ishikawa cells. In pre-malignant obese endometrium from patients with high serum IL-6 levels, attenuated pro-inflammation signaling was seen compared with that from patients with low serum IL6 level: expression of IL1A (FC=-2.21, p=0.001), IRF8 (FC=-1.83, p=0.012), GAGE1 (FC=-3.49, p=0.028), and LBP (FC=-2.03, p=0.038) were decreased. Compared with pre-malignant obese endometrium, more regulatory T cell (Tregs, 0.1276 vs 0.077, p=0.04), and less eosinophils (0.003 vs 0.022, p=0.028) in the stroma, and more neutrophils (0.0145 vs. 0, p=0.02) in the tumor glands were observed in obese EC, implicating immuno-suppression in OEC. Conclusion: Due to the elevated systemic pro-inflammation status, pre-malignant obese endometrium demonstrated activated IL-6 signaling. IL-6 induced cell signaling varied by cellular microenvironment. In pre-malignant endometrium from obese women with high systemic IL-6 level, attenuated inflammation signaling was observed compared to those with low serum IL6 levels. Immuno-suppression was implicated in obese EC. Citation Format: Qian Zhang, Brenda Melendez, Xiaoping Su, Mikayla Bowen, Joseph Celestino, Melinda Sue Yates, Karen Lu. IL6 signaling in pre-malignant obese endometrium and endometrial cancer [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B025.

Association of IL-4 (− 590 C/T) and IL-6 (− 174 G/C) gene polymorphism in South Indian CKD patients

AimThe present study was undertaken to examine the role of IL-4 (− 590 C/T) (rs2243250) and IL-6 (− 174G/C) (rs1800795) polymorphism and the serum levels of IL-4 and IL-6 in chronic kidney disease (CKD).MethodsThe IL-4 (− 590C/T) and IL-6 (− 174 G/C) polymorphisms were genotyped in 132 CKD patients and 161 controls using PCR–RFLP. Serum IL-4 and IL-6 quantifications were performed by ELISA.ResultsSignificant susceptible associations of CT genotype (OR = 4.56; p < 1.84 × 10–9) and T allele (OR = 1.56; p < 0.010) of IL-4 (− 590C/T) and CC genotype (OR = 2.63; p < 0.032) of IL-6 (− 174G/C) were observed for CKD. The CC genotype (OR = 0.27; p < 9.314 × 10–7) and C allele (OR = 0.63; p < 0.010) of IL-4 (− 590 C/T) revealed strong protective associations. Five-fold increased levels were observed for both IL-6 (p < 0.0001) and IL-4 (p < 0.0043) cytokines in CKD patients than the controls. The IL-4 serum levels (pg/ml) increased significantly in patients with CT and TT genotypes of IL-4 (− 590 C/T) than the controls (6.18 ± 1.80 vs. 3.33 ± 0.48 and 6.14 ± 1.96 vs. 3.21 ± 0.56 respectively). For IL-6 (− 174 G/C) polymorphism, the patients with CC genotype (6.50 ± 1.30 vs. 3.49 ± 1.39) revealed with higher IL-6 serum levels followed by GC genotype (5.00 ± 1.91 vs. 4.01 ± 1.74).ConclusionThe genotypes of IL-4 (590 C/T) and IL-6 (174 G/C) polymorphisms contribute differential susceptibility in south Indian CKD patients. A fivefold increased serum levels of IL-4 (anti-inflammatory) and IL-6 (pro- and anti-inflammatory) cytokines were documented in CKD patients. There observed an opposite trend in disease association for these two cytokines and associated SNPs with CKD in south India.

A Study on the Relationship between Clinical Course and Serum IL-6 Level in Neonatal Calves with Diarrhoea

The aim of the study is to investigate the relationship between clinical course and serum IL-6 level in neonatal calves with diarrhea. The study material consisted of 40 calves in the neonatal period. The calves were divided into 4 groups: group I (healthy, control, n=10), group II (with mild diarrhea, n=10), group III (with moderate diarrhea, n=10) and group IV (with severe diarrhea, n=10). The breed, age, sex and clinical findings of the calves were recorded. Etiological analysis was performed on stool samples taken from calves. Haematological analyzes were performed on the blood samples taken and serum IL-6 levels were determined using the ELISA test kit. WBC and NEU numbers of calves with diarrhea in group II, group III and group IV were found to be numerically higher than healthy calves in group I (P˃0.05). Calves in group II (239.76±11.05), group III (293±48.7) and group IV (300±25.06) had higher serum IL-6 levels than calves in group I (211.58±10.07) (P˂ 0.01). While IL-6 levels of group IV were higher than group III (P˃0.05), IL-6 levels of group III and IV were higher than group II (P˂0.01). According to the data obtained from this study, it was concluded that serum IL-6 is an important marker that can be used in the follow-up of the disease in diarrheic neonatal calves.

The Prognostic Utility of Cytokines in Hospitalized COVID-19 Patients.

The severity of COVID-19 relies on several factors, but the overproduction of pro-inflammatory cytokines remains a central mechanism. The aim of this study was to investigate the predictive utility of interleukin (IL)-6, IL-8, IL-10, IL-12, tumor necrosis factor alpha (TNF-α), and interferon gamma (IFN-γ) measurement in patients with COVID-19. We prospectively enrolled 181 adult patients with COVID-19 admitted to the 1st Infectious Disease County Hospital Târgu Mureș from December 2020 to September 2021. Serum cytokine levels were measured and correlated with disease severity, need for oxygen therapy, intensive care unit (ICU) transfer, and outcome. We found significantly higher serum levels of IL-6, IL-8, and IL-10 in patients with severe COVID-19 and in those with a fatal outcome. The logistic regression analysis showed a significant predictive value for IL-8 regarding disease severity, and for IL6 and IL-10 regarding ICU transfer and fatal outcome. Serum levels of IL-6, IL-8, and IL-10 were significantly increased in patients with COVID-19, but their predictive value regarding disease severity and the need for oxygen therapy was poor. We found IL-6 and IL-10 to have a good predictive performance regarding ICU transfer and fatal outcome.

Serum Cytokine Profiles in Patients with Rheumatoid Arthritis Before and After Treatment with Methotrexate.

Rheumatoid arthritis (RA) is an inflammatory autoimmune illness affecting around 1% of the population globally. Cytokines have a crucial role in the pathogenesis of RA. The objectives of the present study were to compare the serum cytokine profiles between methotrexate (MTX)-treated and MTX-naive RA patient groups, MTX-treated RA patient group and healthy controls, and MTX-naive RA patient group and healthy controls. Enzyme linked immunosorbent assay (ELISA) kits were used to quantify the serum concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, IL-17, IL-6, interferon-gamma (IFN-γ), and IL-10 in 80 RA patients (48 MTX treated and 32 MTX naive) and 80 healthy controls. For all cytokine assays, absorbance was measured at 450 nm using a microplate reader (Bio-Rad). Independent sample t-test was used to compare the serum cytokine concentrations between the study groups using SPSS version 25. MTX-treated RA patient group had significantly reduced serum levels of TNF-α (36.13 ± 17.64 versus 45.82 ± 23.07, *P = 0.037), IL-17 (307.85 ± 151.74 versus 435.42 ± 241.19, **P = 0.006), and IFN-γ (414.93 ± 212.13 versus 527.15 ± 269.61, *P = 0.041) compared to MTX-naive RA patients. Both MTX-treated and MTX-naive RA patient groups had significantly high serum levels of TNF-α, IL-1β, IL-17, IL-6, IFN-γ, and IL-10 when compared to healthy controls (***P < 0.001). Downregulation of the serum concentrations of certain key cytokines, viz. TNF-α, IL-17, and IFN-γ, demonstrates the anti-inflammatory effect of MTX in RA patients.

Sarcopenia: Inflammatory and Humoral Markers in Older Heart Failure Patients.

Sarcopenia is highly prevalent in heart failure (HF) patients, and the involvement of biomarkers in its pathophysiology is suggested, but little has been studied concerning HF sarcopenic patients. To evaluate the association between inflammatory and humoral markers with sarcopenia, as well as the impact of sarcopenia on quality of life and functional capacity in older HF patients. In this cross-sectional study, 90 outpatient HF patients, aged ≥ 60 years, were evaluated for sarcopenia (EWGSOP2 diagnostic criteria), inflammation (high-sensitive C-reactive protein [hs-CRP], Interleukin-6 [IL-6], tumor necrosis factor alpha [TNF-α]) and humoral markers (total testosterone and insulin-like growth factor-1 [IGF-1]), physical activity (International Physical Activity Questionnaire), quality of life (Minnesota Living with Heart Failure Questionnaire), and functional capacity (6-minute walk test). The adopted level of significance was p<0.05. Patients had a mean age of 69.4 ± 7.2 years, 67.8% were male, with left ventricular ejection fraction (LVEF) of 35.9 ± 11.9% and 22 (24.4%) were sarcopenic. Age (73.1 ± 8.1 and 68.3 ± 6.5 years; p= 0.006), body mass index (BMI) (23.1 ± 2.8 and 28.2 ± 4.2 kg/m2; p <0.001), and LVEF (29.9 ± 8.8 and 37.9 ± 12.1%; p= 0.005) were different between groups with and without sarcopenia, respectively. After adjusting for age, ethnicity, BMI, LVEF, and the use of angiotensin converting enzyme inhibitors/angiotensin receptor blockers, sarcopenia was associated with higher serum levels of IL-6 and worse functional capacity. In HF patients, sarcopenia was associated with IL-6 levels and functional capacity.

Factors affecting clinical outcome in COVID-associated rhino-orbito-cerebral mucormycosis (CAROM) patients—An ambispective, single-arm, observational study

BackgroundCOVID-associated Rhino-Orbito-Cerebral Mucormycosis (CAROM) appeared as an epidemic in India during the second wave of the COVID-19 pandemic during the months of March to May 2021. Though many reports have highlighted cross sectional and short-term attributes related to CAROM, long term follow up data is sparse. ObjectiveThis report aims to analyze the follow-up outcomes in consecutive patients presenting to us during the epidemic. Patients and methodsThis was an ambispective observational analytical study, recruiting the consecutive patients admitted to our tertiary care centre during the period of the CAROM epidemic. The mortality rate during the follow-up and various factors affecting survival were studied using univariable and multivariable statistics with the Stata 14.0 software. ResultsOf the 189 patients studied, eight were lost to follow-up. The outcome analysis was performed for the 181 patients. 93.6 % (162/173) of the patients had diabetes. The All-cause mortality was 45 % (81/181), while the ROCM-specific mortality was found to be 24 % (46/181) at a median follow-up of 176 days (IQR: 21–217 days). With univariable analysis, increasing age, higher serum IL-6 levels, presence of additional comorbidities (in addition to Diabetes and hypertension), bilateral disease, skin necrosis, palatal involvement, infratemporal fossa involvement, and impaired vision/ocular movements were found to be associated with increased mortality. However, on multivariable analysis, only 1) increasing age, 2) raised serum IL-6 levels, and 3) bilateral disease were predictive of increased mortality. Surgical debridement (endoscopic, palatal removal, orbital exenteration, neurosurgical intervention) was associated with significantly reduced mortality on both univariable and multivariable analysis. ConclusionOur intermediate-term follow-up data showed advanced age at presentation, raised IL-6 levels, and bilateral sinonasal involvement to be predictive of increased mortality, while surgical debridement is significantly protective from mortality in CAROM patients.

Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes

BackgroundThe development of diffuse large B-cell lymphoma (DLBCL), a prevalent subgroup of non-Hodgkin lymphoma (NHL), potentially involves various cytokines. We aimed to determine the correlation between deregulated serum levels of cytokines and clinical features and investigate their impact on the prognosis of patients with DLBCL. MethodsWe conducted a retrospective study of 77 patients with newly diagnosed DLBCL to explore the relationships between different cytokines, adverse clinical features, and poor outcomes. The Mann–Whitney U test was used to compare the cytokine profiles between patients with DLBCL and healthy controls. The Kaplan–Meier method was used to analyze the probability of survival, and the log-rank tests were used to evaluate the differences between survival curves. The Cox proportional hazards regression model was used to performed univariate and multivariate analyses to evaluate prognostic variables for survival analyze. ResultsSerum levels of interleukin-2 (IL-2), tumor necrosis factor (TNF)-α, IL-6, IL-10, and IFN-γ were significantly elevated in patients with untreated DLBCL. Serum levels of IL-6 and IL-10 were significantly higher in patients with an International Prognostic Index (IPI) of 3–5, bone marrow involvement, serum levels of LDH ≥ 250 U/L, and β2-microglobulin (β2-MG) levels ≥ 2.3 mg/L. Patients with B symptoms only had higher serum IL-10 levels, whereas patients with a partial response or no response to treatment had significantly elevated serum levels of IL-6 as well as IL-10. Significant positive correlations were observed between the levels of IL-6 and IL-10 with those of β2-MG and LDH. Patients with levels of IL-6 ≥ 4.5 or IL-10 ≥ 5.0 pg/mL, as well as combined elevated IL-6 and IL-10 levels, exhibited shorter progression-free survival and overall survival. Additionally, univariate and multivariate analyses revealed that serum levels of IL-6 ≥ 4.5 pg/mL and IL-10 ≥ 5.0 pg/mL and IPI 3–5 were independent prognostic factors for relapse and survival in patients with DLBCL. ConclusionsPre-treatment serum IL-6 and IL-10 levels in patients with newly diagnosed DLBCL might be powerful markers for determining treatment response and predicting the prognosis of DLBCL.