Clinical Significance Of Interleukin-6 Research Articles

Clinical significance of interleukin-6, total bilirubin, CD3 + CD4 + T cells counts in the acute exacerbation of connective tissue disease-associated interstitial lung disease: a cross-sectional study

ObjectiveInterstitial lung disease (ILD) is a severe complication of connective tissue disease (CTD) that can significantly impact patients' prognosis and quality of life. However, the current diagnostic arena lacks reliable biomarkers for detecting and monitoring the progression and exacerbation of CTD-ILD. This study aimed to investigate the clinical value of 12 serum cytokines in the diagnosis of CTD-ILD and prediction of the risk of acute exacerbation (AE) in this disease.MethodsThis study was a cross-sectional investigation. Ninety-one hospitalized CTD patients were allocated into two groups: CTD-ILD group (n = 61) and CTD-non-ILD group (n = 30), and 30 sex-age matched healthy volunteers were enrolled as controls. The serum concentrations of interferon (IFN)-α, IFN-γ, tumor necrosis factor (TNF)-α, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, and IL-1β were measured by Luminex suspension arrays. Logistic regression was employed to determine the significance of variables in the occurrence of AE-CTD-ILD. A nomogram was constructed to visualize the independent variables.ResultsElevated levels of IL-6, IL-8, and TNF-α were observed and compared in the CTD-ILD group with CTD-non-ILD (all P < 0.05). Similarly, the levels of IL-6, IL-8 and TNF-α were higher in the acute exacerbation (AE-CTD-ILD) group compared with stable CTD-ILD (S-CTD-ILD) (P < 0.001, P < 0.001, and P = 0.022). Significant correlations between serum IL-6 and PaO2/FiO2 ratio (r = − 0.463, P < 0.001), percent predicted forced vital capacity (FVC%; r = − 0.362, P < 0.05), and total ground-glass opacity (GGO) score (r = 0.439, P < 0.001) were observed in CTD-ILD patients. Multivariate logistic regression analysis revealed that elevated IL-6 levels, total bilirubin (TBil), and decreased CD3 + CD4 + T cells counts were independent risk factors for the occurrence of AE-CTD-ILD (OR = 1.121, P = 0.024; OR = 1.865, P = 0.047; OR = 0.983, P = 0.037, respectively). Furthermore, by employing these three variables in combination for the prediction of AE status, their collective impact surpasses the independent effects of any single biomarker.ConclusionsElevated levels of serum IL-6, IL-8, and TNF-α were associated with the complication of ILD in CTD patients and the occurrence of AE in CTD-ILD patients. IL-6 could be a promising serum biomarker of severity and the occurrence of AE in CTD-ILD patients. The combination of the three variables (IL-6 level, TBil and CD3 + CD4 + T cells) predicted the AE-CTD-ILD better.

Expression and Clinical Significance of IL-6, IL-10, TNF-α and β2-MG in Multiple Myeloma Patients with Different Results of Blood Separation

To investigate the expression level and the clinical significance of serum interleukin-6(IL-6) , IL-10, tumor necrosis factor α(TNF-α) and β2-microglobulin(β2-MG) in multiple myeloma(MM) patients with different blood separation results. The clinical data of 124 newly diagnosed MM patients (76 cases of IgG type, 48 cases of IgA type) treated in our hospital from October 2015 to October 2019 were enrolled and analyzed. The blood samples were divided into control group (the order from top to bottom is serum, separator gel and red blood cells) and abnormal group (the order from top to bottom is serum, red blood cells, separator gel and red blood cells) according to the blood separation result. The differences of expression level in serum IL-6, IL-10, TNF-α and β2-MG were compared between the two groups, and the changes of blood separation result and different indexes were analyzed after treatment. Abnormal separation results were found in 21 cases (16.94%), including 13 cases of IgG type and 8 cases of IgA type. The levels of serum IL-6, IL-10, TNF-α and β2-MG in abnormal group were significantly higher than those in control group (P<0.05) . After treatment, 85 patients in control group (103 cases) achieved complete remission (CR) or very good partial remission (VGPR) and partial remission(PR). The results of blood separation showed no change. 18 patients achieved less than PR, and the separation result in 5 patients changed from normal to abnormal separation. The blood separation of 9 patients with CR and VGPR in abnormal group (21 cases) were changed from abnormal to normal. 8 patients achieved PR, and the separation result in 6 patients were changed from abnormal to normal and 2 cases showed no change, while the blood separation showed no changes in 4 cases MM patients who achieved less than PR in abnormal group. The expression levels of IL-6, IL-10, TNF-α and β2-MG of patients in control group transformed to abnormal blood separation result after treatment showed significantly higher than those before treatment (P<0.05) , and the levels of IL-6 and β2-MG were significantly lower in the patients with out change in blood separation results than those before treatment (P<0.05). The serum levels of IL-6, IL-10, TNF-α and β2-MG of patients in abnormal group transformed to normal blood separation after treatment were significantly lower than those before treatment (P<0.05), and the serum levels of IL-6, IL-10, TNF-α and β2-MG in abnormal group with no changes in blood separation results showed not significantly different from those before treatment (P>0.05). Abnormal separation phenomenon can be found after centrifugation in patients with multiple myeloma. The expression levels of serum IL-6, IL-10, TNF-α and β2-MG in MM patients with different blood separation results are different, which suggesting different degrees of tumor burden. The changes of blood separation result and levels of IL-6, IL-10, TNF-α and β2-MG after treatment can predict the therapeutic effect, and also provide the experimental basis for the evaluation of disease condition and prognosis of patients with different blood separation results.

Clinical significance of interleukin-6 in severity and relapse in type 1 autoimmune pancreatitis

Clinical significance of interleukin-6 in severity and relapse in type 1 autoimmune pancreatitis

The clinical significance of interleukin-6 in heart failure: results from the BIOSTAT-CHF study.

Inflammation is a central process in the pathophysiology of heart failure (HF), but trials targeting tumour necrosis factor (TNF)-α were largely unsuccessful. Interleukin (IL)-6 is an important inflammatory mediator and might constitute a potential pharmacologic target in HF. However, little is known regarding the association between IL-6 and clinical characteristics, outcomes and other inflammatory biomarkers in HF. We thus aimed to identify and characterize these associations. Interleukin-6 was measured in 2329 patients [89.4% with a left ventricular ejection fraction (LVEF) ≤ 40%] of the BIOSTAT-CHF cohort. The primary outcome was all-cause mortality and HF hospitalization during 2years, with all-cause, cardiovascular (CV), and non-CV death as secondary outcomes. Approximately half (56%) of all included patients had plasma IL-6 values greater than the previously determined 95th percentile of normal values at baseline. Elevated N-terminal pro-brain natriuretic peptide, procalcitonin and hepcidin, younger age, TNF-α/IL-1-related biomarkers, or having iron deficiency, atrial fibrillation and LVEF > 40% independently predicted elevated IL-6 levels. IL-6 independently predicted the primary outcome [HR (95% confidence interval) per doubling: 1.16 (1.11-1.21), P < 0.001], all-cause mortality [1.22 (1.16-1.29), P < 0.001] and CV as well as non-CV mortality [1.16 (1.09-1.24), P < 0.001; 1.31 (1.18-1.45), P < 0.001], but did not improve discrimination in previously published risk models. In a large, heterogeneous cohort of HF patients, elevated IL-6 levels were found in more than 50% of patients and were associated with iron deficiency, reduced LVEF, atrial fibrillation and poorer clinical outcomes. These findings warrant further investigation of IL-6 as a potential therapeutic target in specific HF subpopulations.

Clinical Significance of Interleukin-6 in the Diagnosis of Sepsis and Discriminating Sepsis Induced by Gram-negative Bacteria.

To discuss the clinical significance of interleukin (IL)-6 in the differential diagnosis of sepsis and its capability of differentiating the sepsis induced by Gram-negative bacteria from that induced by Gram-positive bacteria. A total of 379 children with sepsis were involved in this study to form the case group, and their C-reactive protein (CRP), procalcitonin (PCT) and IL-6 levels before antibiotics and after recovery were checked. Receiver operating characteristic curve was applied to evaluate the significance of CRP, PCT and IL-6 in the differential diagnosis of sepsis and their capability of differentiating the sepsis induced by Gram-negative bacteria from that induced by Gram-positive bacteria. When these 3 indicators were applied to the differential diagnosis of sepsis, the area under the curve (AUC) of IL-6, PCT and CRP was 0.881, 0.877 and 0.754, respectively. The combination of IL-6 and PCT presented highest diagnostic efficiency. CRP, PCT and IL-6 levels in children with sepsis induced by Gram-negative bacteria were significantly higher than those in children with sepsis induced by Gram-positive bacteria. CRP, IL-6 and PCT are applicable to the differential diagnosis of sepsis and differentiating the sepsis induced by Gram-negative bacteria from Gram-positive bacteria. Appropriate combinations of these indicators are capable of increasing differential diagnosis efficiency. These indicators can be used as markers of antibiotics usage, but whether they can be used as markers to withdraw antibiotics is still needed to be observed.

Clinical significance of interleukin-6 and -8 in patients with chronic periodontal disease and acute exacerbation of chronic obstructive pulmonary disease

Objective: To investigate the serum levels of interleukin (IL)-6 and -8 in patients with chronic periodontal disease and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and the possible relationship between IL-6 and IL-8 with two diseases. Methods: A total of 40 cases of healthy subjects (control group 1) from graduate school of Anhui Medical University, and 120 cases (40 cases in each of the 3 groups) of eligible patients were collected, of which 40 were patients with chronic periodontal disease and AECOPD (experimental group) from Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University and Anhui NO.2 Provincial People's Hospital, 40 were patients with chronic periodontal disease (control group 2) from Department of Stomatology, The First Affiliated Hospital of Anhui Medical University, 40 were patients with AECOPD (control group 3) from Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University. The clinical indicators of all subjects were collected, including tooth mobility degree, probing depth (PD), bleeding index (BI), attachment level (AL), vital capacity max (VC Max), forced expiratory volume in first second (FEV1) and forced expiratory volume in first second to forced vital capacity (FEV1/FVC) ratio. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum levels of IL-6 and IL-8 in the subjects of four groups. Results: The attachment levels had no significant differences between experimental group and control group 2 (P>0.05). The pulmonary function indices of experimental group including VC MAX% pre[(56.1±11.1)%], FEV1 %pre [(44.8±12.2)%], FEV1/FVC(%) [(56.8±11.4)%] were significantly different from those in control group 3 [(66.3±10.1)%, (53.0±10.4)%, (66.5±8.2)%, respectively]. The IL-6 levels of experimental group, control groups 1, 2 and 3 were (14.4±3.9), (2.1±1.1), (4.8±1.9) and (8.6±1.4) ng/L, respectively. And the IL-8 levels were (35.3±33.3), (4.8±1.7), (9.7±3.3) and (15.6±9.6) ng/L. In experimental group the IL-6 and IL-8 levels were significantly higher than those in control groups 1, 2, and 3 (P<0.01). In control group 2 and 3 the IL-6 and IL-8 levels were significantly higher than that in control group 1 (P< 0.01). Conclusions: The IL-6 and IL-8 levels of experimental group were significantly increased. IL-6 and IL-8 may be associated with the development of periodontal disease and AECOPD closely.

Clinical significance of interleukin-6 in diagnosis of lung, oral, esophageal, and gall bladder carcinomas.

Chronic inflammation predisposes to cancer. Cytokines play an essential role in cancer pathogenesis. Interleukin-6 (IL-6) is a pleiotropic cytokine that enables growth and differentiation of tumors. The effects of IL-6 are mediated by signal transducers and activators of transcription 3 (STAT3). STAT3 deficiency reduced tumor incidence and growth while STAT3 hyperactivation has an opposite effect; also it negatively regulates p53 gene. IL-6/STAT3 signaling is crucial in carcinogenesis linked to inflammation. Increased IL-6 levels are observed in cancer. Studies investigating the role of IL-6 is limited. This study aims at determining IL-6 levels in lung, oral, esophageal, and gallbladder cancer patients. Subjects consisted of 175 patients with lung, oral, gall bladder, and esophageal cancers. The patients included 68 females and 107 males with an average age of 52 years. Fifty healthy individuals served as controls. IL-6 was detected by electrochemiluminescent immunoassay principle. IL-6 values were determined in 175 (21 lung, 55 oral, 17 esophageal and 82 gallbladder) cancer patients. Of these, 147/175 (18 lung, 43 oral, 13 esophageal and 73 gallbladder) cancer patients (84%) showed higher IL-6 levels as compared to control group (normal range: <7 pg/ml). This indicates a significant correlation between IL-6 overexpression and cancer development, highlighting the significance of IL-6 in oral, lung, esophageal, and gallbladder carcinomas. IL-6 may be used as a tumor marker for cancer diagnosis. It may be a clinically significant predictor and may represent a target for cancer treatment. However, to definitely conclude this, further extensive studies would be required.

Clinical significance of interleukin-6, tumor necrosis factor-α and high-sensitivity C-reactive protein in neonates with hypoxic-ischemic encephalopathy.

The present study aimed to investigate the potential roles of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and high-sensitivity C-reactive protein (Hs-CRP) in the progression and prognosis of neonatal hypoxic-ischemic encephalopathy (HIE). The observation group comprised 74 neonates with HIE and the control group comprised 74 healthy neonates. The serum levels of IL-6, TNF-α and Hs-CRP were measured in the patients with HIE and the normal control infants. The correlations between the variances in the levels of these inflammatory cytokines and the different clinical gradings and prognoses of the disease were analyzed. The data revealed significant upregulation of the serum levels of IL-6, TNF-α and Hs-CRP in patients with HIE. The increase in the levels of these inflammatory mediators correlated with the severity of the disease and also had a positive correlation with the prognosis of the disease. In conclusion, high levels of IL-6, TNF-α and Hs-CRP were observed in neonatal patients with HIE. Thus, these inflammatory mediators may play a role in the progression and prognosis of the disease.

Clinical Significance of Interleukin-6 (Il-6) Gene Polymorphism and Il-6 Serum Level in Pancreatic Adenocarcinoma and Chronic Pancreatitis

The aim of our study was to assess the clinical significance of -174G/C Il-6 gene polymorphism and Il-6 serum level in patients with pancreatic adenocarcinoma (PA) and chronic pancreatitis (CP). The study included 41 with pancreatic adenocarcinoma, 56 with chronic pancreatitis, and 50 healthy volunteers, hospitalized between 2003 and 2006. Il-6 serum levels were measured with an enzyme-linked immunoassay and Il-6 gene polymorphism was studied in DNA isolated from peripheral blood. In PA and CP patients Il-6 serum levels were significantly higher than in the control group (P < 0.01). The levels of Il-6 in the patients with tumor size >or=3.5 cm were higher than that in patients with smaller tumors (P < 0.01). The elevated Il-6 levels were also correlated with the presence of liver metastases (P < 0.01). Mean Il-6 serum level was significantly higher in patients homozygous G/G for -174 Il-6 gene compared with patients with at least one C allele. Our findings indicate that -174G/C Il-6 gene polymorphism influences circulating Il-6 levels. Increased Il-6 serum levels may be correlated with tumor size and the presence of liver metastases in patients with pancreatic adenocarcinoma.

Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease

Interleukin-6 (IL-6) is proinflammatory cytokine that produces multifunctional effects. It is also involved in the regulation of immune reactions, hematopoiesis and inflammatory state. Interleukin-6 has been shown to be associated with tumor progression including inhibition of cancer cells apoptosis and stimulation of angiogenesis. Anti-IL-6 therapy is a new strategy in the inflammatory autoimmune diseases and cancer. Clinical studies have shown elevated serum IL-6 concentrations in patients with endometrial cancer, non-small cell lung carcinoma, colorectal cancer, renal cell carcinoma, breast and ovarian cancer. Serum IL-6 levels correlate with tumor stage, and survival of patients. In this article we have focused on a role of IL-6 as a prognostic factor in several malignancies such as colorectal cancer, breast cancer, gastric cancer and pancreatic cancer.

Clinical significance of interleukin-6 (IL-6) in the spread of gastric cancer: role of IL-6 as a prognostic factor

It is becoming clear that various cytokines are associated with the spread of cancer cells. The purpose of this study was to compare interleukin (IL)-6 levels in patients with gastric cancer to elucidate the role of IL-6 in predicting the spread of tumors. In 60 patients, we assessed the correlation of serum IL-6 (pg/ml) with stage, histological findings, hepatic metastasis, and related factors (hepatocyte growth factor [HGF], IL-1beta, tumor necrosis factor [TNF]-alpha, and transforming growth factor [TGF]-beta1). We also investigated the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, as well as the association between IL-6 elevation and outcome. Finally, we examined the expression of IL-6 in tumor tissue. Significant relationships were seen between serum IL-6 and stage, depth of tumor invasion (pT), lymphatic invasion (ly), venons invasion (v)*, lymph node metastasis (pN), hepatic metastasis (cH), and HGF (P < 0.01; *P < 0.05). With regard to the diagnostic significance of the IL-6 level for advanced gastric cancer and lymph node metastasis, when the cutoff value of IL-6 was set at 1.97 pg/ml, the sensitivity was 81.8% and 87.5%; specificity was 66.7% and 58.3%; and accuracy was 77.1% and 72.9%, respectively. The 1- and 3-year cumulative survival rates for patients with an IL-6 value of more than 1.97 pg/ml (69.0% and 43.4%, respectively) were significantly lower than those for patients with an IL-6 value of 1.97 pg/ml or less (94.4% and 87.2%, respectively; P < 0.05). Immunohistochemical staining was positive for IL-6 in the cytoplasm of cancer cells. We suspect that IL-6 is involved in cancer invasion and lymph node and/or hepatic metastasis. Our results indicate that IL-6 could be used as a prognostic factor for survival.

Clinical significance of interleukin-6 and interleukin-6 receptor expressions in oral squamous cell carcinoma.

Recent studies showed that interleukin-6 (IL-6) played a role in tumor development. However, available information about the prognostic significance of IL-6 and IL-6 receptors (IL-6R) for oral squamous cell carcinoma (OSCC) is limited. Eighty-six patients with OSCC were enrolled. Immunohistochemical staining was used to determine IL-6R expression and in-situ hybridization for IL-6 mRNA transcripts in surgical specimens. Clinicopathologic correlation was evaluated by chi-square test and survival by log rank test. Expression rates of IL-6R and IL-6 mRNA transcripts in tumor specimens were 73.3% and 54.7%, much higher than those in nontumor mucosa (p <.001). IL-6R overexpression was associated with larger tumors and more advanced histologic grade (p <.05). The presence of IL-6 mRNA transcripts was inversely correlated with distant metastasis, lymph node involvement, and second primary SCC (p <.05) and predicted better survival (p =.007). IL-6-IL-6R coexpression was rather high in OSCC, and IL-6 mRNA transcript expression might influence patient survival. The biologic role of IL-6-IL-6R coexpression in OSCC needs additional investigation.

Study of interleukin-6 and tumor necrosis factor-alpha levels in maternal serum and amniotic fluid of patients with premature rupture of membranes.

To study the change and clinical significance of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels in the maternal serum and amniotic fluid of pregnant women with chorioamnionitis and with premature rupture of membranes. Twenty-six normal-term pregnant women formed the control group, and forty-six pregnant women with premature rupture of membranes were enrolled for the study. Maternal serum and amniotic fluid IL-6 and TNF-alpha levels were measured using a sensitive radioimmunoassay and enzyme-linked immunosorbent assay (ELISA); chorioamnionitis was diagnosed by fetal membrane pathology. The maternal serum IL-6 levels and amniotic fluid IL-6 and TNF-alpha levels were higher than those of the control (P < 0.01). There was a significant relationship between maternal serum IL-6 and maternal serum and amniotic fluid IL-6 and TNF-alpha with the time of the premature rupture of membranes, i.e. the longer the time, the higher the maternal serum and amniotic fluid IL-6 and TNF-alpha. There were 12 patients with chorioamnionitis in premature rupture of membranes and their maternal serum and amniotic fluid IL-6 and TNF-alpha levels were higher than that of non-chorioamnionitis patients (P < 0.01-0.05). IL-6 and TNF-alpha levels in maternal and amniotic fluids are a valuable index in identification of the chorioamnionitis in patients with premature rupture of membranes.