Preoperative Immune Cell Dysregulation Accompanies Ovarian Cancer Patients into the Postoperative Period.

Ovarian cancer (OC) poses a significant global health challenge with high mortality rates, emphasizing the need for improved treatment strategies. The immune system's role in OC progression and treatment response is increasingly recognized, particularly regarding peripheral blood mononuclear cells (PBMCs) and cytokine production. This study aimed to investigate PBMC subpopulations (T and B lymphocytes, natural killer cells, monocytes) and cytokine production, specifically interleukin-1 beta (IL-1ß), interleukin-4 (IL-4), interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-12 (IL-12), and tumor necrosis factor alpha (TNFα), in monocytes of OC patients both preoperatively and during the early postoperative period. Thirteen OC patients and 23 controls were enrolled. Preoperatively, OC patients exhibited changes in PBMC subpopulations, including decreased cytotoxic T cells, increased M2 monocytes, and the disbalance of monocyte cytokine production. These alterations persisted after surgery with subtle additional changes observed in PBMC subpopulations and cytokine expression in monocytes. Considering the pivotal role of these altered cells and cytokines in OC progression, our findings suggest that OC patients experience an enhanced pro-tumorigenic environment, which persists into the early postoperative period. These findings highlight the impact of surgery on the complex interaction between the immune system and OC progression. Further investigation is needed to clarify the underlying mechanisms during this early postoperative period, which may hold potential for interventions aimed at improving OC management.

Effects of venoactive drug therapy and ovarian vein interventions on vasoactive neuropeptide and cytokine levels in patients with pelvic venous disorders.

OBJECTIVE: To study and compare the effects of venoactive drug (VAD) therapy and ovarian vein embolization or resection (OVE or OVR, accordingly) on the levels of vasoactive peptides and cytokines in patients with pelvic venous disorders (PeVD). METHODS: The study included 70 consecutive female patients with PeVD symptoms, such as chronic pelvic pain (CPP), dyspareunia, dysuria, and vulvar varicosities. Based on the results of clinical examination and duplex ultrasound (DUS) of the pelvic veins, the patients were allocated to the VAD therapy (n=38) or OVE/OVR (n=32). Additionally, the enzyme-linked immunosorbent assay (ELISA) tests were performed to determine levels of calcitonin gene-related peptide (CGRP), substance P (SP), interleukins 6 and 8 (IL-6, IL-8) and monocyte chemotactic protein-1 (MCP-1) after a 2-month course of VAD therapy and at 3 months after OVE/OVR. RESULTS: The VAD therapy was associated with a significant decrease in CPP in 84% of patients with PeVD and isolated lesions of the parametrial veins (PVs) and uterine veins (UVs). VAD had no significant effect on the pelvic venous reflux. No changes in the CGRP, SP, IL-6, IL-8 and MCP-1 levels were detected after treatment. At 3 months after OVE or OVR, all patients with PeVD and combined lesions of the ovarian veins (OVs), PVs and UVs reported almost complete relief of CPP. Along with elimination of reflux in OVs, the disappearance of reflux in PVs and UVs was noted. A decrease in the CGRP and SP levels was observed (0.7 ± 0.1 ng/mL and 0.12 ± 0.02 ng/mL before treatment; 0.5 ± 0.12 ng/mL and 0.09 ± 0.06 ng/mL after treatment, respectively; all P<0.05). No changes in cytokine levels were revealed. CONCLUSION: Treatment with VAD is associated with the CPP relief, but has no significant effect on the CGRP, SP, IL-6, IL-8, and MCP-1 levels. OVE/OVR results in the CPP relief, elimination of the pelvic venous reflux and a significant decrease in the CGRP and SP levels, but does not change cytokine levels.

Exploring Galectin Interactions with Human Milk Oligosaccharides and Blood Group Antigens Identifies BGA6 as a Functional Galectin-4 Ligand.

Galectins (Gals), a family of multifunctional glycan-binding proteins, have been traditionally defined as ß-galactoside binding lectins. However, certain members of this family have shown selective affinity towards specific glycan structures including human milk oligosaccharides (HMOs) and blood group antigens. In this work, we explored the affinity of human galectins (particularly Gal-1, -3, -4, -7 and -12) towards a panel of oligosaccharides including HMOs and blood group antigens using a complementary approach based on both experimental and computational techniques. While prototype Gal-1 and Gal-7 exhibited differential affinity for type I vs. type II Lac/LacNAc residues and recognized fucosylated neutral glycans, chimera-type Gal-3 showed high binding affinity towards poly-LacNAc structures including LNnH and LNnO. Notably, the tandem-repeat human Gal-12 showed preferential recognition of 3-fucosylated glycans, a unique feature among members of the galectin family. Finally, Gal-4 presented a distinctive glycan-binding activity characterized by preferential recognition of specific blood group antigens, also validated by saturation transfer difference nuclear magnetic resonance (STD-NMR) experiments. Particularly, we identified oligosaccharide blood group A type 6 (BGA6) as a biologically relevant Gal-4 ligand, which specifically inhibited IL-6 secretion induced by this lectin on human peripheral blood mononuclear cells. These findings highlight unique determinants underlying specific recognition of HMOs and blood group antigens by human galectins, emphasizing the biological relevance of Gal-4-BGA6 interactions, with critical implications in the development and regulation of inflammatory responses.

Long-term clinicopathological characteristics of TAFRO syndrome and its relapse: a case series study.

Introduction: This study aimed to analyze the clinical course of TAFRO syndrome in patients through extended follow-up, focusing on recurrent cases and long-term remission. Methods: This was a retrospective case series study. We assessed the clinical course of patients diagnosed with TAFRO syndrome between January 2012 and September 2022 at Toranomon Hospital or Toranomon Hospital Kajigaya, excluding those patients who died during the initial hospitalization. Results: Twelve patients were included. Baseline characteristics, laboratory findings, treatment modalities, and outcomes were assessed. During the median follow-up period of 1474 days, two patients experienced recurrence following a reduction in tocilizumab (TCZ) dose, whereas two achieved remission for >400 days without TCZ treatment. The remaining eight patients maintained remission under the continued TCZ therapy. Recurrence diagnosis was complicated by the non-simultaneous presentation of the five manifestations of TAFRO syndrome. The patients who experienced recurrence showed milder manifestations and faster recovery than the initial onset. Glomerular endotheliopathy was evident in kidney biopsies during recurrence, which was similar to the initial presentation. In a case where only inflammation preceded other manifestation, a kidney biopsy was pivotal in distinguishing TAFRO syndrome relapse from other inflammatory conditions such as infection. Pretreatment serum IL-6 levels were within the reference range only in patients who experienced long-term remission without TCZ treatment. Conclusions: This is the first study to perform kidney biopsies on recurrent TAFRO cases, highlighting recurrence after TCZ dosage reduction, non-simultaneous manifestation of symptoms, the utility of kidney biopsies in recurrence diagnosis, and potential non-IL-6 pathogenesis factors. Pretreatment serum IL-6 levels may help identify patients suitable for maintenance therapy without TCZ. Further investigation is warranted to identify stratified treatment approaches based on individual etiologic factors.

Association of serum interleukin-6 with negative symptoms in stable early-onset schizophrenia.

BACKGROUND: Accumulating evidence suggests that the inflammatory cytokine interleukin-6 (IL-6) contributes to the pathophysiology of psychiatric disorders. However, there was no study concerning the relationship between IL-6 concentrations and clinical features in the chronic phase of early-onset schizophrenia (EOS). AIM: To investigate the relationship between serum IL-6 concentration and the clinical features of EOS. METHODS: We measured serum IL-6 Levels from 74 patients with chronic schizophrenia, including 33 with age at onset < 21 years (EOS group) and 41 with onset ≥ 21 years in [adult-onset schizophrenia (AOS) group], and from 41 healthy controls. Symptom severities were evaluated using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Serum IL-6 concentrations were higher in both EOS and AOS groups than healthy controls (F = 22.32, P < 0.01), but did not differ significantly between EOS and AOS groups (P > 0.05) after controlling for age, body mass index, and other covariates. Negative symptom scores were higher in the EOS group than the AOS group (F = 6.199, P = 0.015). Serum IL-6 concentrations in the EOS group were negatively correlated with both total PANSS-negative symptom score (r = -0.389, P = 0.032) and avolition/asociality subscore (r = -0.387, P = 0.026). CONCLUSION: Patients with EOS may have more severe negative symptoms than those with adult-onset schizophrenia during the chronic phase of the illness. IL-6 signaling may regulate negative symptoms and its avolition/asociality subsymptoms among the early-onset chronic schizophrenic patients.

Interleukin-6 in Sepsis-Promising but Yet to Be Proven.

How to cite this article: Sinha S. Interleukin-6 in Sepsis-Promising but Yet to Be Proven. Indian J Crit Care Med 2024;28(7):629-631.

Diagnostic Potential of Serum Interleukin-6 in Predicting Bacteremia in Adult Patients with Sepsis: A Prospective Observational Study.

Background: This study aimed to assess the potential of serum interleukin-6 (IL-6) as a diagnostic marker in predicting bacteremia and to determine its association with severity and outcome among sepsis patients. Materials and methods: A prospective observational study was conducted, comprising a cohort of 118 patients admitted to the ICU with suspected sepsis from January 2019 to April 2020. Results: Among the 108 patients analyzed, 60 (55.6%) were bacteremic and 48 (44.4%) were nonbacteremic. Of 60 patients with bacteremia, 13 (21.6%) had sepsis and 47 (78.3%) had septic shock. In predicting bacteremia, the area under the curve (AUC) for IL-6 was 0.512 [95% CI, 0.400-0.623]. The AUC for IL-6 in differentiating sepsis from septic shock was 0.724 [95% CI, 0.625-0.823]. The sensitivity and specificity for predicting bacteremia for IL-6 were 66% and 67%, respectively (p < 0.001). Multivariate analysis revealed that C-reactive protein (CRP) (p = 0.04) and APACHE II score (p = 0.025) were significant predictors of bacteremia, whereas lactate (p = 0.04), and APACHE II score (p < 0.001) were significant predictors of sepsis severity. Patients with elevated levels of procalcitonin PCT (p = 0.024), APACHE II (p = 0.003), and SOFA (p = 0.002) scores had significantly higher mortality rates. Conclusion: C-reactive protein and APACHE II score, lactate and APACHE II score, and PCT, SOFA, and APACHE II scores performed better in predicting bacteremia, sepsis severity, and clinical outcome, respectively compared with IL-6. How to cite this article: Reddy PRV, Cherukuri M, Eshwara VK, Kudru CU, Prabhu RVK. Diagnostic Potential of Serum Interleukin-6 in Predicting Bacteremia in Adult Patients with Sepsis: A Prospective Observational Study. Indian J Crit Care Med 2024;28(7):637-644.

The SASP factor IL-6 sustains cell-autonomous senescent cells via a cGAS-STING-NFκB intracrine senescent noncanonical pathway.

Senescent cells produce a Senescence-Associated Secretory Phenotype (SASP) that involves factors with diverse and sometimes contradictory activities. One key SASP factor, interleukin-6 (IL-6), has the potential to amplify cellular senescence in the SASP-producing cells in an autocrine action, while simultaneously inducing proliferation in the neighboring cells. The underlying mechanisms for the contrasting actions remain unclear. We found that the senescence action does not involve IL-6 secretion nor the interaction with the receptor expressed in the membrane but is amplified through an intracrine mechanism. IL-6 sustains intracrine senescence interacting with the intracellular IL-6 receptor located in anterograde traffic specialized structures, with cytosolic DNA, cGAS-STING, and NFκB activation. This pathway triggered by intracellular IL-6 significantly contributes to cell-autonomous induction of senescence and impacts in tumor growth control. Inactivation of IL-6 in somatotrophic senescent cells transforms them into strongly tumorigenic in NOD/SCID mice, while re-expression of IL-6 restores senescence control of tumor growth. The intracrine senescent IL-6 pathway is further evidenced in three human cellular models of therapy-induced senescence. The compartmentalization of the intracellular signaling, in contrast to the paracrine tumorigenic action, provides a pathway for IL-6 to sustain cell-autonomous senescent cells, driving the SASP, and opens new avenues for clinical consideration to senescence-based therapies.

Association of Renal Impairment with Interleukin-6 Levels on Clinical Outcomes among COVID-19 Patients in a Tertiary Government COVID-19 Referral Hospital.

Objective: The objective of the study is to determine the association of renal impairment (AKI or CKD) with IL-6 levels on mortality, intubation, and length of hospitalization among COVID-19 positive patients. Methods: This is a retrospective cohort study involving chart review of COVID-19 patients with IL-6 levels and admitted from May 2020 to April 2021. The KDIGO criteria was used for determining renal impairment. The subsequent data processing and analysis was carried out using the statistical software, Stata 13. Results: A total of 1,120 charts were included with patients classified as having AKI (33%), CKD (14%), and no renal impairment (58%). Overall mortality and need for intubation were 27% and 30%, respectively, with average length of stay at 12 days. The IL-6 values were divided into low (0 to less than 51 pg/mL), intermediate (51 to 251 pg/mL), and high (greater than 251 pg/mL) tertiles, which showed acceptable sensitivity and specificity for mortality and need for intubation. Conclusion: The presence of renal impairment (CKD or AKI) with increasing IL-6 levels had an effect of increasing risk of adverse outcomes; however, within tertile groups, the presence of renal impairment did not significantly change the risk of adverse outcomes. The tertile groups have acceptable sensitivity and specificity for clinical use.

Predictive value of interleukin-6 combined with serum neuron-specific enolase on the prognosis of acute ischemic stroke.

OBJECTIVE: To explore the prognostic value of interleukin-6 (IL-6) combined with serum neuron specific enolase (NSE) in arterial atherosclerotic ischemic stroke. METHODS: 116 patients with arterial atherosclerotic ischemic stroke admitted to the emergency ward of our Hospital were retrospectively analyzed. According to the score of modified Rankin scale (mRS) at 90 days after discharge, the patients were divided into the poor prognosis group (mRS > 2, n = 32) and the good prognosis group (mRS ≤ 2, n = 84). Activities of Daily Living (ADL) was used to evaluate the level of independence in activities of daily living after treatment. RESULTS: The NIHSS score (14.91 ± 5.20 vs. 9.43 ± 4.30, P < 0.001), IL-6 (11.30 ± 3.11 vs. 6.75±1.28, P < 0.001) and NSE levels (12.47 ± 4.69 vs. 6.42 ± 1.32, P<0.001) in poor prognosis group were higher than those in the good prognosis group. At 90 days post-discharge, 100 % of the good prognosis group had ADL scores over 60, while in the poor prognosis group, 46.88 % scored 40-60, 40.63 % scored 20-40, 9.38 % scored under 20, and 3.13 % died. The AUC of NSE was 0.906 (95 % CI: 0.847-0.965, P < 0.001), the best cut-off value was 7.445 ng/mL, and the sensitivity and specificity were 75.0 % and 82.1 %, respectively. The AUC for IL-6 combined with NSE increased to 0.965 (95 %CI: 0.934-0.997, P < 0.001), and the sensitivity and specificity increased to 80.2 % and 92.9 %, respectively. CONCLUSION: IL-6 ≥ 6.805 pg/mL and NSE ≥ 7.445 ng/mL were independently associated with poor prognosis in patients with AIS, and the combined testing of the two indicators had a higher predictive value. These results suggested that the combined assay of IL-6 and NSE could be a novel marker for predicting poor prognosis in AIS.

Characterizing the Linkage of Systemic Hypoxia and Angiogenesis in High-Grade Glioma to Define the Changes in Tumor Microenvironment for Predicting Prognosis.

High-grade gliomas (HGG) comprising WHO grades 3 and 4 have a poor overall survival (OS) that has not improved in the past decade. Herein, markers representing four components of the tumor microenvironment (TME) were identified to define their linked expression in TME and predict the prognosis in HGG, namely, interleukin6 (IL6, inflammation), inducible nitric oxide synthase(iNOS), heat shock protein-70 (HSP70, hypoxia), vascular endothelial growth receptor (VEGF), and endothelin1 (ET1) (angiogenesis) and matrix metalloprotease-14 (MMP14) and intercellular adhesion molecule1 (ICAM1, extracellular matrix). To establish a non-invasive panel of biomarkers for precise prognostication in HGG. Eighty-six therapy-naive HGG patients with 45 controls were analyzed for the defined panel. Systemic expression of extracellular/secretory biomarkers was screened dot-immune assay (DIA), quantified by ELISA, and validated by immunocytochemistry (ICC). Expression of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 was found to be positively associated with grade. Quantification of circulating levels of the markers by ELISA and ICC presented a similar result. The biomarkers were observed to negatively correlate with OS (p < 0.0001). Cox-regression analysis yielded all biomarkers as good prognostic indicators and independent of confounders. On applying combination statistics, the biomarker panel achieved higher sensitivity than single markers to define survival. The intra-association of all seven biomarkers was significant, hinting of a cross-talk between the TME components and a hypoxia driven systemic inflammation upregulating the expression of other components. This is a first ever experimental study of a marker panel that can distinguish between histopathological grades and also delineate differential survival using liquid biopsy, suggesting that markers of hypoxia can be a cornerstone for personalized therapy. The panel of biomarkers of iNOS, HSP70, IL-6, VEGF, ET1, MMP14, and ICAM1 holds promise for prognostication in HGG.

An evaluation of inflammatory and endothelial dysfunction markers as determinants of peripheral arterial disease in those with diabetes mellitus.

The most serious long-term effects of diabetes is peripheral artery disease (PAD) which increases the chance of developing diabetic foot ulcers, gangrene and even lower limb amputation. The clinical manifestations of PAD which are typically not revealed until symptoms like intermittent claudication, rest pain and ischemic gangrene develop, are not present in majority of diabetes mellitus patients with PAD due to diabetic peripheral neuropathy. Therefore, current study is aimed to evaluate the inflammatory and endothelial dysfunction markers with their correlation to biomarkers that can help for in-time diagnosis and efficient prognosis of developing diabetes-associated PAD. Enzyme-linked immunosorbent assay was used to evaluate the interlukin-6, interlukin-8, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in PAD with diabetes group, diabetic group and healthy individual group while biomarkers were measured by kit method. It was observed that serum IL-6, IL-8, ICAM and VCAM levels in type II diabetes mellitus (T2DM) with PAD patients were increased significantly (85.93, 597.08, 94.80 and 80.66) as compared to T2DM patients (59.52, 231.34, 56.88 and 50.19) and healthy individuals (4.81, 16.93, 5.55 and 5.16). The overall means for the parameters, IL-6, IL-8, ICAM, VCAM, urea, S/creatinine, CK-MB, AST, ALT, cholesterol, triglyceride, HDL, LDL, PT, aPTT, INR, HbA1C, and CRP within all groups were significantly (P < 0.05) different from each other. Therefore, it was concluded that the change in IL-6, IL-8, ICAM and VCAM can serve as an accurate diagnostic indicator and successful treatment.

Assessment value of interleukin-6, procalcitonin, and C-reactive protein early kinetics for initial antibiotic efficacy in patients with febrile neutropenia: A prospective study.

BACKGROUND: This study aims to investigate the early kinetics of interleukin 6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) on initial antibiotic efficacy in hematological disorder patients with febrile neutropenia (FN). METHODS: A total of 40 patients with 43 episodes of FN were enrolled and divided into initial antibiotic effective group (IAE group, n = 24) and initial antibiotic ineffective group (IAI group, n = 19). The levels of IL-6, PCT, and CRP before antibacterial treatment (T0), and 12 h (T1), 24 h (T2), 48 h (T3), and 72 h (T4) post-antibacterial treatment were determined, respectively. Furthermore, the receiver operating characteristic curve (ROC) analysis was performed to evaluate the clinical value of indicators. RESULTS: In IAE group, the IL-6 levels gradually decreased from T0 to T4, and the CRP levels significantly decreased at 48 to 72 h, whereas both IL-6 and CRP remained at high levels in the IAI group. The PCT levels in both groups increased at the early stage of anti-infection (T1-T2) and reached to peak at T1-T2 in effective group. ROC curve analysis identified IL-6 as a predictive biomarker for initial antibiotic efficacy at 12, 48, and 72 h after treatment, with the AUC of 0.698, 0.744, and 0.821, respectively. In addition, CRP demonstrated predictive ability of initial antibiotics against infection at 24, 48, and 72 h after therapy, with the AUC of 0.724, 0.741, and 0.797, respectively. ROC curve analysis of percentage changes demonstrated that IL-6 percentage change showed predictive ability of antibiotic efficacy at the early stage, and both the IL-6 and CRP percentage changes showed the predictive ability of antibiotic efficacy 48 or 72 h after antibiotics therapy. CONCLUSION: This study confirmed IL-6 and CRP levels, and the percentage change in IL-6 as the biomarkers for initial antibiotic efficacy prediction in hematological disorder patients with FN.

The role of interleukin-6 family cytokines in cancer cachexia.

Cachexia is a wasting syndrome that manifests in more than half of all cancer patients. Cancer-associated cachexia negatively influences the survival of patients and their quality of life. It is characterized by a rapid loss of adipose and skeletal muscle tissues, which is partly mediated by inflammatory cytokines. Here, we explored the crucial roles of interleukin-6 (IL-6) family cytokines, including IL-6, leukemia inhibitory factor, and oncostatin M, in the development of cancer cachexia. These cytokines have been shown to exacerbate cachexia by promoting the wasting of adipose and muscle tissues, activating mechanisms that enhance lipolysis and proteolysis. Overlapping effects of the IL-6 family cytokines depend on janus kinase/signal transducer and activator of transcription 3 signaling. We argue that the blockade of these cytokine pathways individually may fail due to redundancy and future therapeutic approaches should target common downstream elements to yield effective clinical outcomes.

Vitamin D3 Supplementation and Aquatic Exercise Combination as a Safe- Efficient Therapeutic Strategy to Ameliorate Interleukin-6 and 10, and Social Interaction in Children with Autism.

Objectives: Increasing evidence demonstrated that there are altered levels of both pro-and anti-inflammatory cytokines in autism spectrum disorder (ASD) and pointed out that immune dysfunction may also relate to social deficits. This study aimed to investigate the effect of aquatic exercise combined with vitamin D supplementation on social interaction and two related cytokines (Interleukin-6 and Interleukin-10) in children with ASD. Materials & Methods: Forty boys with ASD (mean age: 10.90; age range: 6-14 years) were randomly assigned to the three interventions (groups 1, 2, and 3) and one control group (each 10 participants). Participants in the group 1 and 3 received a 10-week aquatic exercise program. Subjects in groups 2 and 3 took orally 50,000 IU of vitamin D3/week. This study evaluated the serum levels of IL-6 and IL-10, as well as the participants' social interaction at baseline and post-intervention. Results: Compared to the control group, all three interventions improved social skills scores (p< 0.001). Surprisingly, the combination strategy could significantly reduce IL-6 and increase IL-10 serum levels in children with ASD. Conclusion: Aqua-based exercise programs combined with vitamin D supplementation are recommended to benefit children with ASD and improve social and communication dysfunction.

Intratumoral Delivery of Genetically Engineered Anti-IL-6 Trans-signaling Therapeutics.

Interleukin-6 (IL-6) is a highly pro-inflammatory cytokine involved in the etiopathology of several inflammatory diseases and cancer. As so, the inhibition of IL-6 signaling pathways has emerged as an attractive therapeutic avenue for the treatment of several chronic diseases. Since IL-6 trans-signaling was described as the pathological branch of IL-6, selective inhibitors were developed. Next-generation variants with increased trans-signaling specificity and potency emerged as great candidates for the treatment of several diseases, with reduced off-target effects. The highly time-consuming and costly processes involving recombinant protein production, however, have hampered the progress of anti-cytokine pharmaceuticals in clinic so far. Herein, we developed gene therapeutic modalities of IL-6-trans-signaling inhibitors as alternatives for sustained recombinant protein secretion. By using an IL-6-dependent lymphoma cell line and xenograft tumor model, we demonstrated the superior inhibitory potential of second-generation anti-IL-6 trans-signaling therapeutic. We compared the efficiency of distinct gene delivery modalities using a bioluminescent biomarker probe and observed consistent protein production via cell-based delivery. When delivered intratumorally, genetically engineered sgp130FlyRFc-secreting cells significantly reduced tumor burden and increased animal survival, representing a promising therapeutic avenue to be explored in clinically relevant gene delivery applications.

Serum interleukin-6 concentration in patients with pemphigus.

Pemphigus is a rare blistering autoimmune disease that damages the integumentary system and lowers the quality of life of patients. Interleukin-6 (IL-6) has been linked to the immunopathogenesis of pemphigus, according to recent research. Thus, the investigation purpose was to assess the function of IL-6 in the development and intensity of pemphigus disease. Between January 2022 and August 2022, a case-series study involving 26 patients with pemphigus vulgaris (PV), four patients with pemphigus foliaceus (PF), and 20 healthy volunteers was carried out at the Ho Chi Minh City Hospital of Dermato-Venereology. Patients with PV and PF had significantly higher serum IL-6 concentrations than healthy volunteers (p<0.001). Patients with a positive Nikolsky sign had significantly higher serum IL-6 concentrations than those with a negative sign (p<0.001). The serum IL-6 concentration and the pemphigus disease area index were found to significantly correlate (r=0.8, p<0.001). According to our findings, IL-6 might be a significant factor in pemphigus development and severity. Thus, novel treatments that specifically target IL-6 could be a good option for managing pemphigus, particularly in its more severe forms.

Exploring the causal relationship between interleukin-6 or C reactive protein and malignant melanoma using a two-sample Mendelian randomization approach.

The goal was to explore the effect of interleukin-6 (IL6) and C reactive protein (CRP) on malignant melanoma (MM) using two-sample Mendelian randomization. Methods: Data for this study were obtained from the IEU Open GWAS project website for genome-wide association study data (GWAS) on interleukin-6, C reactive protein levels and malignant melanoma. Inverse variance weighted (IVW) method was mainly used and supplemented with MR-Egger regression and weighted median. Finally, horizontal multivariate validity and heterogeneity tests were performed to assess the stability and reliability of the results. Results: The results of univariate two-sample MR analyses showed no significant effect of CRP on MM: inverse variance weighting method (OR=0.999, 95% CI: 0.998-1.001, P=0.343), MR-Egger regression (OR= 1.000, 95% CI: 0.998-1.001, P= 0.180), and weighted median method (OR= 0.999, 95% CI: 0.997 to 1.000, P= 0.583), and weighted model (OR= 0.999, 95% CI: 0.998 to 1.001, P= 0.328). Also,IL-6 had no significant effect on MM: inverse variance weighting method (OR= 1.001, 95% CI: 0.999 to 1.002, P=0.461), MR-Egger regression (OR= 1.000, 95% CI: 0.997 to 1.004, P= 0.910), weighted median method (OR= 1.000, 95% CI: 0.998 to 1.002, P= 0.749), and weighted mode (OR= 1.000, 95% CI: 0.998 to 1.002, P= 0.820). Conclusion: There was no causal relationship between C-reactive protein and IL-6 on the risk of malignant melanoma.

Prognostic value of interleukin-6 serum levels in hospitalized COVID-19 patients: A case-control study in Iran.

Introduction: The coronavirus pandemic (COVID-19) is an infectious disease with a high mortality rate that is challenging to treat. Cytokine storm is a crucial factor leading to acute respiratory distress syndrome in COVID-19 patients. Identifying factors that predict the severity of the disease may be primarily prognostic to guide drug therapy. The objective of this study was to investigate the prognostic role of interleukin 6 (IL-6) in the hospitalized patients infected with COVID-19. Methods: This case-control study was conducted from October 2019 to April 2020 at Shahid Faqihi hospital in Iran. Fifty hospitalized COVID-19 patients and 50 healthy individuals were included while controlling demographics and comorbidities. IL-6 serum levels were measured and compared based on demographic characteristics (age, sex) and comorbidities in the case and control groups. Spearman rank correlation coefficient was also used to analyze the correlations between IL-6 levels and lung involvement in COVID-19 patients. Moreover, some laboratory parameters were compared based on the percentage of lung involvement. Results: The level of IL-6 in the case group was significantly higher than the control (p ˂ 0.001). We observed a positive and significant correlation between the level of IL-6 and the severity of lung involvement (r = 0.0.79, p < 0.01). The median level of IL-6 in patients who showed more than 75% lung involvement was 573 (IQR = 320-850). Conclusion: Available evidence suggests that high levels of IL-6 are associated with the severity of COVID-19. According to the results, it could be proposed that inhibition of IL-6 might be a target for therapeutic managements to reduce mortality in the patients with COVID-19.

Abdominal wound length influences the postoperative serum level of interleukin-6 and recovery of flatus passage among patients with colorectal cancer.

Introduction: A mini-laparotomy for colorectal cancer (CRC) has been reported to shorten postoperative ileus (POI) and hospital stay. Interleukin-6 (IL-6) plays a role in intestinal tissue inflammation, leading to POI. This study investigated the effects of abdominal wounds and IL-6 levels on POI in patients having CRC surgery. Materials and methods: Forty-three patients with CRC underwent bowel resection. Serum samples were collected preoperatively and at 2, 24, and 48 h after surgery for cytokine quantification by ELISA. Clinical data, including time from surgery to first passage of flatus and postoperative hospital stay, demographic and pathological data, and routine blood tests, were compared statistically with abdominal wound length and the postoperative increments of cytokines (designated as Δ). Results: The length of the abdominal wound showed a significant correlation with clinical variables (length of operation time, time of first flatus passage, and length of postoperative hospital stay) and cytokine variables (IL-6(Δ2 h), IL-8(Δ2 h) and IL-10(Δ2 h). Linear regression analysis showed that the abdominal wound length significantly influenced the operation time, time of first flatus passage, and length of postoperative hospital stay (p < 0.001). The length of the abdominal wound showed a significant influence on the IL-6(Δ2 h) and IL-8(Δ2 h) (p < 0.001, respectively) but no influence on IL-10(Δ2 h). IL-6(Δ2 h), but not IL-8(Δ2 h), significantly influenced the time to first flatus passage and length of hospital stay (p = 0.007, p = 0.006, respectively). The mini-laparotomy approach (wound length <7 cm) led to significantly shortened operation time, time of first flatus passage, length of postoperative stay (p = 0.004, p = 0.003, p = 0.006, respectively) as well as reduced postoperative increment of IL-6(Δ2 h) (p = 0.015). The mini-laparotomy for anterior resection surgery significantly influenced operation time, time of first passage of flatus, length of postoperative stay, and IL-6(Δ2 h). Conclusion: Our study is the first to report the complex interaction among the length of the abdominal wound, IL-6 serum level, recovery of the first passage of flatus, and postoperative hospital stay. These results suggest that smaller abdominal wounds and smaller postoperative IL-6 increments were associated with faster recovery of flatus passage and shorter hospital stays.