Elevated Serum Interleukin-6 Research Articles

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

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

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

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

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

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

Association Between Interleukin-6 and Head and Neck Squamous Cell Carcinoma: A Systematic Review.

Interleukin-6 (IL-6) is a proinflammatory cytokine which plays an important role in several regulatory mechanisms of cancer. Moreover, experimental and clinical studies have reported that IL-6 targeted therapies might provide significant benefits for cancer treatment. The purpose of this systematic review is to evaluate IL-6 activity in patients with head and neck squamous cell carcinoma (HNSCC). A systematic review of the association between serum, saliva and tumor IL-6 and HNSCC was developed on PubMed/Medline in the publication range from January 1995 to January 2019. Our literature analysis demonstrated that overexpression and elevated serum and/or saliva IL-6 concentrations in patients with HNSCC are related to poor survival and oncological outcomes. Although there is a correlation between IL-6 concentrations and tumorigenicity, it is noteworthy that IL-6 targeted therapies are generally performed in vitro and in experimental studies. Therefore, prospective, randomized clinical trials are required that focus on IL-6 targeted therapies for the treatment of HNSCC.

Cathelicidin-related antimicrobial peptide alleviates alcoholic liver disease through inhibiting inflammasome activation.

Alcoholic liver disease (ALD) is associated with gut dysbiosis and hepatic inflammasome activation. While it is known that antimicrobial peptides (AMPs) play a critical role in the regulation of bacterial homeostasis in ALD, the functional role of AMPs in the alcohol-induced inflammasome activation is unclear. The aim of this study was to determine the effects of cathelicidin-related antimicrobial peptide (CRAMP) on inflammasome activation in ALD. CRAMP knockout (Camp-/-) and wild-type (WT) mice were subjected to binge-on-chronic alcohol feeding and synthetic CRAMP peptide was administered. Serum/plasma and hepatic tissue samples from human subjects with alcohol use disorder and/or alcoholic hepatitis were analyzed. CRAMP deficiency exacerbated ALD with enhanced inflammasome activation as shown by elevated serum interleukin (IL)-1β levels. Although Camp-/- mice had comparable serum endotoxin levels compared to WT mice after alcohol feeding, hepatic lipopolysaccharide (LPS) binding protein (LBP) and cluster of differentiation (CD) 14 were increased. Serum levels of uric acid (UA), a Signal 2 molecule in inflammasome activation, were positively correlated with serum levels of IL-1β in alcohol use disorder patients with ALD and were increased in Camp-/- mice fed alcohol. In vitro studies showed that CRAMP peptide inhibited LPS binding to macrophages and inflammasome activation stimulated by a combination of LPS and UA. Synthetic CRAMP peptide administration decreased serum UA and IL-1β concentrations and rescued the liver from alcohol-induced damage in both WT and Camp-/- mice. In summary, CRAMP exhibited a protective role against binge-on-chronic alcohol-induced liver damage via regulation of inflammasome activation by decreasing LPS binding and UA production. CRAMP administration may represent a novel strategy for treating ALD. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Poststreptococcal acute glomerulonephritis in a girl with renal cell carcinoma: possible pathophysiological association

The severity of the poststreptococcal acute glomerulonephritis is considered to be modulated by the immune response of each individual, although there had been few reports regarding specific factors. Renal cell carcinoma is a cancer frequently associated with paraneoplastic syndrome, characterized by fever, leukocytosis, elevated cytokines, and elevated hormone levels. All of these symptoms resolve after tumor resection. A girl with renal cell carcinoma developed renal failure rapidly, which resolved promptly right after nephrectomy for the carcinoma. She was diagnosed as having poststreptococcal acute glomerulonephritis according to the results of pathological and serological examinations. In addition, elevated serum interleukin-6 level before the surgery was detected. Six and a half years after the diagnosis, the patient's renal function was within normal range and she was tumor free. Because of the quick resolution of her renal dysfunction after the nephrectomy, paraneoplastic syndrome induced by renal cell carcinoma seemed to play a key role in the accentuation of poststreptococcal acute glomerulonephritis.

Impact of baseline serum IL-8 on metastatic hormone-sensitive prostate cancer outcomes in the Phase 3 CHAARTED trial (E3805).

The immunosuppressive cytokine interleukin- 8 (IL-8), produced by tumor cells and some myeloid cells, promotes inflammation, angiogenesis, and metastasis. In our discovery work, elevated serum IL-8 at androgen deprivation therapy (ADT) initiation portended worse overall survival (OS). Leveraging serum samples from the phase 3 CHAARTED trial of patients treated with ADT +/- docetaxel for metastatic hormone-sensitive prostate cancer (mHSPC), we validated these findings. Two hundred and thirty-three patients had serum samples drawn within 28 days of ADT initiation. The samples were assayed using the same Mesoscale Multiplex ELISA platform employed in the discovery cohort. After adjusting for performance status, disease volume, and de novo/metachronous metastases, multivariable Cox proportional hazards models assessed associations between IL-8 as continuous and binary variables on OS and time to castration-resistant prostate cancer (CRPC). The median IL-8 level (9.3 pg/ml) was the a priori binary cutpoint. Fixed-effects meta-analyses of the discovery and validation sets were performed. Higher IL-8 levels were prognostic for shorter OS (continuous: hazard ratio [HR]2.2, 95% confidence interval [CI]: 1.4-3.6, p = .001; binary >9.3: HR 1.7, 95% CI: 1.2-2.4, p = .007) and time to CRPC (continuous: HR2.3, 95% CI: 1.6-3.3, p < .001; binary: HR 1.8, 95% CI: 1.3-2.5, p < .001) and independent of docetaxel use, disease burden, and time of metastases. Meta-analysis including the discovery cohort, also showed that binary IL-8 levels >9.3 pg/ml from patients treated with ADT alone was prognostic for poorer OS (HR1.8, 95% CI: 1.2-2.7, p = .007) and shorter time to CRPC (HR1.4, 95% CI: 0.99-1.9, p = .057). In the phase 3 CHAARTED study of men with mHSPC at ADT initiation, elevated IL-8 portended worse survival and shorter time to castration-resistant prostate cancer independent of docetaxel administration, metastatic burden, and metachronous versus de novo metastatic presentation. These findings support targeting IL-8 as a strategy to improve mHSPC outcomes.

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019.

The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019. Multicenter prospective observational study. ICU. Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group). Daily measurement of serum inflammatory cytokines. Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1β, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao2/Fio2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao2/Fio2 (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1β on the day of diagnosis. The inverse relationship between serum interleukin-6 and Pao2/Fio2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-β or tumor necrosis factor-α.

Interleukin 6, interleukin 17, disease-related and contextual factor association with depression, and its severity in patients with rheumatoid arthritis.

Depression is very prevalent in rheumatoid arthritis (RA) compared with the general population and may be associated with poor clinical outcomes. Identifying factors associated with depression could improve outcomes for this at risk group. However, few studies have comprehensively examined the association of contextual and disease-related factors as well as pro inflammatory cytokines interleukin 6 (IL-6) and interleukin 17 (IL-17) with depression in RA. Therefore, we aimed to identify the factors significantly associated with depression and severe depression in RA, thus providing a reference for applying clinical care interventions for patients with RA. An observational cross-sectional study was conducted on 120 RA patients. Potential determinants included contextual and disease-related factors and laboratory variables. Enzyme-linked immunosorbent assay was used to measure serum IL-6 and IL-17 levels. Depression was assessed using the Arabic version of the Beck Depression Inventory-II questionnaire. A total of 120 patients were included, and up to 67.5% had some degree of depression with 60% having moderate to severe depression. The severity of disease activity of RA (DAS28-ESR (OR, 1.63; 95% CI, 0.899-3.755), HAQ scores (OR, 1.27; 95% CI, 0.702-2.933), and VAS scores for pain (OR, 2.2; 95% CI, 1.251-5.223)), besides elevated serum IL-6 (OR, 1.51; 95% CI, 0.832-3.475), IL-17 (OR, 1.28; 95% CI, 0.706-2.947), and CRP levels (OR, 1.20; 95% CI, 0.923-2.882) were significantly associated with depression and its severity in the multivariate analysis. Depression is frequent in RA and is strongly associated to elevated serum IL-6, IL-17, CRP levels, and disease activity-related factors. Key Points • RA patients are at increased risk of developing depression, particularly if their level of disease activity scores, serum IL-6, and IL-17 levels increases. • Patient characteristics associated with depression in RA include living without family, without employments, and with co-morbid hypertension, while RA disease factors are pain, functional disability, and high disease activity. • A multidisciplinary cooperative approach to RA patient care with regular assessments of these factors associated with depression should be incorporated into routine care programs to improve patients' self care capabilities and mitigate or prevent depression in these patients.

Elevated serum YKL-40, IL-6, CRP, CEA, and CA19-9 combined as a prognostic biomarker panel after resection of colorectal liver metastases.

The inflammatory biomarkers, YKL-40 and interleukin-6 (IL-6), are elevated in patients with metastatic colorectal cancer. We examined their associations with relapse-free survival and overall survival in combination with serum C-reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA19-9) in patients with colorectal liver metastases. Altogether 441 consecutive patients undergoing liver resection at Helsinki University Hospital between 1998 and 2013 were included in the study. Pre- and postoperative YKL-40 and IL-6 were determined from serum samples with commercially available enzyme-linked immunosorbent assay (ELISA) kits, and CRP, CEA, and CA19-9 by routine methods. Associations between these biomarkers and relapse-free and overall survival were examined using Cox regression analysis. Patients with 2-5 elevated biomarkers were at an increased risk of relapse compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.37, 95% CI 1.1-1.72) or postoperatively (HR 1.54, 95% CI 1.23-1.92). Patients with 2-5 elevated biomarkers were also at an increased risk of death compared to those with 0-1 elevated biomarkers, preoperatively (HR 1.76, 95% CI 1.39-2.24) or postoperatively (HR 1.83, 95% CI 1.44-2.33). The results suggest that a protein panel of the inflammatory biomarkers YKL-40, IL-6, and CRP, and the cancer biomarkers CEA and CA19-9 might identify patients that benefit from more aggressive treatment and surveillance, although the additional value of IL-6 and CRP in this aspect is limited.

Interleukin-6 receptor blocking with intravenous tocilizumab in COVID-19 severe acute respiratory distress syndrome: A retrospective case-control survival analysis of 128 patients

In cases of COVID-19 acute respiratory distress syndrome, an excessive host inflammatory response has been reported, with elevated serum interleukin-6 levels. In this multicenter retrospective cohort study we included adult patients with COVID-19, need of respiratory support, and elevated C-reactive protein who received intravenous tocilizumab in addition to standard of care. Control patients not receiving tocilizumab were matched for sex, age and respiratory support. We selected survival as the primary endpoint, along with need for invasive ventilation, thrombosis, hemorrhage, and infections as secondary endpoints at 30 days. We included 64 patients with COVID-19 in the tocilizumab group and 64 matched controls. At baseline the tocilizumab group had longer symptom duration (13 ± 5 vs. 9 ± 5 days) and received hydroxychloroquine more often than controls (100% vs. 81%). The mortality rate was similar between groups (27% with tocilizumab vs. 38%) and at multivariable analysis risk of death was not significantly influenced by tocilizumab (hazard ratio 0.61, 95% confidence interval 0.33–1.15), while being associated with the use at baseline of non invasive mechanical or invasive ventilation, and the presence of comorbidities. Among secondary outcomes, tocilizumab was associated with a lower probability of requiring invasive ventilation (hazard ratio 0.36, 95% confidence interval 0.16–0.83; P = 0.017) but not with the risk of thrombosis, bleeding, or infections. The use of intravenous tocilizumab was not associated with changes in 30-day mortality in patients with COVID-19 severe respiratory impairment. Among the secondary outcomes there was less use of invasive ventilation in the tocilizumab group.

Can vitamin C and interleukin 6 levels predict preterm premature rupture of membranes: evaluating possibilities in North Indian population.

ObjectiveWe aimed to evaluate the relation between plasma ascorbic acid levels and the occurrence of preterm premature rupture of membranes (PPROM) and whether patients with ascorbic acid deficiency have predisposition to microbial invasion, as revealed by serum interleukin-6 (IL-6) levels and confirmed by placental culture sensitivity evaluation.MethodsThis controlled study involved 50 women with PPROM at gestational age between 28 and 36.6 weeks. Fifty patients with uncomplicated pregnancy and intact membranes were observed as control group. Serum ascorbic acid and IL-6 levels were evaluated for PPROM group subjects and controls, matched by their gestational age and body mass index. Repeat samples for IL-6 were taken after 48 hours of admission in PROM group subjects and at the onset of labor in controls. Placental membranes were sent for culture sensitivity evaluation after delivery.ResultsThe mean plasma level of ascorbic acid was 0.60±0.35 mg/dL and 1.18±0.43 mg/dL in the PPROM and control groups, respectively, showing significant difference. Plasma IL-6 level rose from 18.18±5.94 pg/mL to 34.32±7.31 pg/mL after 48 hours of admission in the PPROM group (P=0.000). Plasma IL-6 level in controls rose from 5.59±4.36 pg/mL at admission to 7.36±3.67 pg/mL at the onset of labor. Membrane culture test results were positive in a total of 40 samples, of which 37 samples were from the PPROM group subjects.ConclusionVitamin C deficiency, when complemented with elevated serum IL-6 level, can predict susceptibility to PPROM in the third trimester; the risk increases in women with prior history of similar pathology.

Elevated serum interleukin-8 is associated with enhanced intratumor neutrophils and reduced clinical benefit of immune-checkpoint inhibitors.

Serum interleukin-8 (IL-8) levels and tumor neutrophil infiltration are associated with worse prognosis in advanced cancers. Here, using a large-scale retrospective analysis, we show that elevated baseline serum IL-8 levels are associated with poor outcome in patients (n = 1,344) with advanced cancers treated with nivolumab and/or ipilimumab, everolimus or docetaxel in phase 3 clinical trials, revealing the importance of assessing serum IL-8 levels in identifying unfavorable tumor immunobiology and as an independent biomarker in patients receiving immune-checkpoint inhibitors.

The role of Interleukin-6 in age-related frailty syndrome

Abstract Aging is accompanied by chronic low-grade inflammation – a term which relates to increase in serum levels of cytokines such as interleukin 6 (IL-6), TNF-α and acute phase proteins such as C-reactive protein. Multiple studies in humans have shown that IL-6 most reliably increases with aging. Frailty is a geriatric syndrome characterized by decrease in physical ability and increased vulnerability to stressors. One of the most consistent findings in frail subjects is an elevation of serum IL-6 but we lack research which delineates is this a causational relationship. We developed a mouse model with inducible IL-6 expression (IL-6TET-ON/+ mice) that enables overexpression of IL-6 following stimulation with doxycycline (dox) administrated in food. IL-6 induction was dose dependent and led to increase in frailty as measured by 30-point murine clinical frailty index. Mice induced to express high levels of IL-6 quickly displayed an increase in frailty index, decrease in muscle grip strength and loss of fat. Mice induced to express 3–4 fold increase in IL-6 similar to frail humans displayed similar changes after months of induction. We measured IL-6 levels in serum and various tissues (gut, muscle, adipose, spleen) of aged (28-month-old) frail mice and adult controls as well as dox fed IL-6TET-ON/+ mice. We observed that IL-6 levels were increased in serums and spleen homogenates of aged mice and IL-6TET-ON/+ mice but not in other tissues. We determined that neutrophils were the main producers of IL-6 and their numbers were higher in spleens of aged and IL-6TET-ON/+ mice compared to adult controls. We conclude that elevated IL-6 serum levels are directly associated with age-related frailty and that spleen neutrophils are likely the main producers of IL-6.

Study of the diagnostic value of interleukin-6 and interleukin-8 in children with acute gastroenteritis.

Gastroenteritis in children is responsible for high morbidity and mortality. Our aim was to determine the serum and fecal levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) in children with acute gastroenteritis of viral and bacterial etiology to assess their utility as diagnostic biomarkers for these infections. In this case-control study, the children were classified according to the pathogen recovered from the stool by bacterial culture or by direct viral antigen detection by enzyme immunoassay (EIA) into 50 children with acute bacterial gastroenteritis and 50 children with acute viral gastroenteritis. In addition, 50 apparently healthy children were included as a control group. Blood and stool samples were subjected to detection of IL-6 and IL-8. There were statistically significant elevations of total leucocytes counts, absolute neutrophils count, C-reactive protein, serum IL-6 and serum IL-8 in children with gastroenteritis compared to healthy children (p<0.001). CRP, serum IL-6 and IL-8 had significantly elevated levels in children with bacterial gastroenteritis compared to viral gastroenteritis. Fecal IL-6 and IL-8 had significantly elevated levels in children with acute gastroenteritis than in healthy control (p<0.001). The area under the curve (AUC) showed that CRP and serum IL-6 could be used as discriminative markers for acute bacterial gastroenteritis in children, in comparison to serum IL-8. Elevated serum IL-6 and CRP can aid in differentiation between viral and bacterial gastroenteritis. Serum IL-8 had limited discrimination ability between viral and bacterial gastroenteritis. Stool levels of IL-6 and IL-8 were elevated in children with viral and bacterial gastroenteritis, however, their assessment by enzyme linked immunosorbent assay had technical limitations to be used as differentiation biomarkers.

Clinical implications of elevated serum interleukin-6 in IgG4-related disease.

IntroductionSome patients with IgG4-related disease (IgG4-RD) exhibit elevated serum interleukin (IL)-6 with excessive inflammatory reactions or with repeating relapse. To date few reports pertaining to clinical implications of elevated serum IL-6 in IgG4-RD patients have been published. The aims of the current retrospective study were to investigate the clinical implications of elevated serum IL-6 in IgG4-RD patients, and to examine whether IL-6 can predict the activity and/or relapse of the disease.Materials and methodsWe examined the clinical picture at the onset of 43 patients who were diagnosed with IgG4-RD in our hospital and were able to measure serum IL-6 before steroid treatment.ResultsThe median level of serum IL-6 was 2.2 pg/mL. There was a significant correlation between IL-6 and C-reactive protein (CRP) level (r = 0.397, p = 0.008), hemoglobin level (r = -0.390, p = 0.010) and albumin level (r = -0.556, p < 0.001). When 43 patients were divided into two groups by using a cut-off IL-6 of 4 pg/mL, the high IL-6 group showed higher age, lower albumin, higher CRP and higher aspartate aminotransferase (AST) (age p = 0.014, albumin p = 0.006, CRP p <0.001, AST p = 0.009). Hepatic swelling and splenomegaly were significantly more prevalent in the high IL-6 group than it was in the low IL-6 group (liver p < 0.001, spleen p = 0.020). Biliary tract involvement tended to admit more in the high IL-6 group (p = 0.060).ConclusionSerum IL-6 level at the onset of IgG4-RD may be significantly correlated with clinical inflammatory parameters and it may also be associated with involvement of the bile duct, liver, and spleen.

Interleukin 6 and disease transformation in chronic myeloid leukemia: A Northeast Indian population study.

Interleukin 6 (IL6) has been suggested to be a valuable prognostic marker in chronic myeloid leukemia (CML). IL6 is a pleiotropic cytokine and plays an important role in immune response, hematopoiesis, and acute phase response. IL6 is regarded as a prominent target for clinical interventions. The aim of the present study was to investigate the serum levels of IL6 in CML to provide greater insight to their role in disease transformation in Indian patients. A total of 50 CML cases and 10 acute lymphocytic leukemia (ALL) cases along with 20 healthy controls were included in the study between 2015 and 2016. About 4 mL blood samples were collected from all cases in plain vial and serum was separated. Levels of IL6 were determined in all cases by enzyme-linked immunosorbent assay. The study suggests that both ALL and CML are associated with significantly elevated serum IL6 level than the healthy control group. Mean levels of serum IL6 are 223.4 ± 53.403 pg/mL in CML, 71.020 ± 29.549 pg/mL in ALL, and 5.360 ± 0.467 pg/mL in healthy control group. Serum IL6 correlated with different phases of CML. Mean IL6 levels are 50.93 ± 29.37 pg/mL in chronic phase (CP), 69.02 ± 22.60 pg/mL in accelerated phase (AP), and 652.77 ± 124.62 pg/mL in blast crisis (BC) phase of CML. In compared to CP and AP, in BC, IL-6 is significantly elevated ( P = 0.00 and 0.00, respectively); however, we did not find a significant difference in IL-6 serum levels between CP and AP ( P = 0.703). Study suggests that the detection of IL6 level in newly diagnosed patient can predict the severity of the disease. There might be association of level of IL6 with the disease transformation.

Probiotic and glutamine treatments attenuate alcoholic liver disease in a rat model.

The pathogenesis underlying alcoholic liver disease (ALD), which is often a result of alcohol abuse, currently remains unclear. Previous studies have reported that enteric dysbiosis serves an important role in the pathogenesis of ALD. The present study aimed to investigate the effects of glutamine and probiotics on a rat model of alcoholic liver disease (ALD). Sixty male Sprague-Dawley rats were randomly divided into 6 groups including control (C), alcohol (M), alcohol + Golden Bifido (T), alcohol + glutamine (G), alcohol + Medilac-S® (N) and alcohol + Golden Bifido + glutamine (L). Histology, body weight (BW), triglycerides (TG), serum aspartate transaminase (AST), alanine aminotransferase (ALT), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), diamine oxidase (DAO), occludin, endotoxin and D-lactate levels were assessed whilst changes in the gut flora were evaluated and compared. Results determined that all probiotic and glutamine treatments elevated the abnormally decreased BW and occludin levels whilst the abnormal elevated serum AST, ALT, TG, IL-6, TNF-α, DAO, endotoxin and D-lactate levels were significantly reduced following chronic ethanol consumption. Histopathological observation of the liver demonstrated that probiotic and glutamine treatments attenuated liver damage induced by alcohol. Moreover, sequencing determined that there was a reduction in Firmicutes as well as an increase in Actinobacteria, Proteobacteria and Porphyromonadaceae abundance in the ALD group compared with the healthy controls. However, these changes were prevented by glutamine and probiotic therapy. In conclusion, the present results suggested that probiotics and glutamine ameliorated ALD by suppressing inflammation and regulating the gut microbiota. Therefore, probiotic and glutamine treatments can potentially serve as therapies for the prevention and treatment of ALD.

Association with elevated level of inflammatory biomarkers and attention deficit in Korean farmers

Inflammation plays an important role in cognitive impairments. This study examined the association of elevated biomarkers, such as C-reactive protein (CRP) and interleukin-6 (IL-6) concentrations, with attentional deficit in Korean farmers. A total of 504 healthy Korean farmers (255 male, mean age 60 years) were enrolled from the Farmers' cohort for Agricultural work-Related Musculoskeletal disorders (FARM) study. Attention was evaluated by measuring the accuracy/error rate and speed when using a computerized Go/No-Go test. Serum level of CRP and IL-6 were measured in specimens. Higher CRP and IL-6 levels were associated with decreased accuracy rate (p < .001). The increased error rate in the Go test was related to an elevated CRP level (p < .001), while the increased error rate of the No-Go test was related to an elevated IL-6 level (p < .001). The correct response time was associated with an increased CRP level in simple and NSAID-adjusted analysis. In the age-adjusted partial correlation analysis, higher CRP and IL-6 levels were associated with a decreased accuracy rate (CRP: Partial r [pr] = −0.171, p < .001; IL-6: pr = −0.196, p < .001). The increased error rate in the Go-test was related to the elevated CRP level (pr = 0.321, p < .001), while increased error rate in the No-Go test was related to the elevated IL-6 level (pr = 0.256, p < .001). Elevated serum CRP and IL-6 were associated with attentional decline, thus suggesting the involvement of inflammation in cognitive impairments in healthy individuals.

Cytokine Effects on the Entry of Filovirus Envelope Pseudotyped Virus-Like Particles into Primary Human Macrophages.

Macrophages are one of the first and also a major site of filovirus replication and, in addition, are a source of multiple cytokines, presumed to play a critical role in the pathogenesis of the viral infection. Some of these cytokines are known to induce macrophage phenotypic changes in vitro, but how macrophage polarization may affect the cell susceptibility to filovirus entry remains largely unstudied. We generated different macrophage subsets using cytokine pre-treatment and subsequently tested their ability to fuse with beta-lactamase containing virus-like particles (VLP), pseudotyped with the surface glycoprotein of Ebola virus (EBOV) or the glycoproteins of other clinically relevant filovirus species. We found that pre-incubation of primary human monocyte-derived macrophages (MDM) with interleukin-10 (IL-10) significantly enhanced filovirus entry into cells obtained from multiple healthy donors, and the IL-10 effect was preserved in the presence of pro-inflammatory cytokines found to be elevated during EBOV disease. In contrast, fusion of IL-10-treated macrophages with influenza hemagglutinin/neuraminidase pseudotyped VLPs was unchanged or slightly reduced. Importantly, our in vitro data showing enhanced virus entry are consistent with the correlation established between elevated serum IL-10 and increased mortality in filovirus infected patients and also reveal a novel mechanism that may account for the IL-10-mediated increase in filovirus pathogenicity.