Search

Background: Although endoscopy is the gold standard to assess disease activity and infliximab efficacy in inflammatory bowel disease (IBD), the invasive, costly, and time-consuming procedure limits its routine applications. We aimed to investigate the clinical value of serum oncostatin M (OSM) as a surrogate biomarker., Methods: Fifty healthy controls, 34 non-IBD patients, and 189 IBD patients who were pre-infliximab treatment (n = 122) or in infliximab maintenance (n = 67) were enrolled. A chemiluminescence immunoassay (CLIA) was constructed to quantify serum OSM concentrations. Receiver operator characteristic (ROC) curve analysis was used to evaluate the performance of blood biomarkers for IBD management., Results: The methodology of CLIA exhibited great analytical performance with a wide linear range of 31.25-25000 pg/mL, a low detection limit of 23.2 pg/mL, acceptable precision, and applicable accuracy. Patients with IBD (121.5 [43.3-249.4] pg/mL, p < 0.001) and non-IBD (72.4 [51.4-129.6] pg/mL, p = 0.005) had higher serum OSM levels than healthy controls (35.8 [23.2-56.4] pg/mL). In the analysis of clinical and endoscopic activity, serum OSM levels were elevated in moderate and severe patients compared to those in remission. IBD patients without mucosal healing had higher serum OSM levels than those with mucosal healing (AUC = 0.843). Besides, serum OSM levels were increased in clinical non-responders (287.3 [127.9-438] pg/mL) compared to responders (24.1 [23.2-53.4] pg/mL, p < 0.001), and showed great recognition ability with an AUC of 0.898., Conclusions: The newly developed methodology of CLIA had great potential for use in the clinic. Elevated serum OSM expression was a promising biomarker of severe disease and infliximab non-response in IBD patients., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: Although several mechanisms have been proposed for the tumor-suppressive effect of exercise, little attention has been given to myokines, even though skeletal muscle is heavily recruited during exercise resulting in myokine surges. We measured resting serum myokine levels before and after an exercise-based intervention and the effect of this serum on prostate cancer cell growth., Methods: Ten prostate cancer patients undertaking androgen deprivation therapy (age, 73.3 ± 5.6 yr) undertook a 12-wk exercise-based intervention including supervised resistance training, self-directed aerobic exercise, and protein supplementation. Body composition was assessed by dual-energy x-ray absorptiometry and muscle strength by the one-repetition maximum method. Fasting blood was collected at baseline and postintervention, and serum levels of myokines-secreted protein acidic and rich in cysteine, oncostatin M (OSM), decorin, insulin-like growth factor-1, and insulin-like growth factor binding protein-3 (IGFBP-3)-were measured. The growth of the prostate cancer cell line DU145 with baseline and postintervention serum was measured., Results: Body weight (P = 0.011), fat mass (P = 0.012), and percent body fat (P = 0.033) were reduced, whereas percent lean mass (P = 0.001) increased, as did strength (leg press, P = 0.006; chest press, P = 0.020) across the intervention. Serum OSM levels (P = 0.020) and relative serum OSM levels (P = 0.020) increased compared with baseline. A significant reduction in DU145 Cell Index (P = 0.012) and growth rate (P = 0.012) was observed after applying postintervention serum compared with baseline serum., Conclusions: This study provides evidence for enhanced myokine expression and tumor-suppressive effects of serum from chronically exercise-trained prostate cancer patients on androgen deprivation therapy., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Sports Medicine.)

The interleukin-6 family cytokine, oncostatin-M (OSM) has been associated with response to tumor necrosis factor-α antagonists (anti-TNFs) in small cohorts of patients with inflammatory bowel disease (IBD). We aimed to evaluate the association between plasma OSM concentrations and response to anti-TNFs (infliximab and adalimumab) in both ulcerative colitis (UC) and Crohn's disease (CD). A retrospective cohort study was conducted in patients with IBD with a history of anti-TNF exposure. Blood samples, collected prior to anti-TNF exposure, were analyzed by enzyme-linked immunosorbent assay for the presence and quantity of OSM. Clinical remission was assessed at 1-year post anti-TNF exposure in addition to the occurrence of surgery, hospitalization, corticosteroid use, and adverse drug events. Lastly the threshold OSM plasma concentration associated with anti-TNF non-response was assessed by receiver operator characteristic (ROC) curve analysis. Patients with IBD (CD, n = 82; UC, n = 40) were assessed. In both UC and CD, mean pre-treatment OSM concentrations were significantly lower in those who achieved clinical remission at 1-year (p < 0.0001). A threshold plasma OSM concentration of 168.7 pg/ml and 233.6 pg/ml respectively separated those who achieved clinical remission at 1-year on an anti-TNF from those who did not in CD and UC respectively (CD: area under the receiver operator characteristic curve, AUROC = 0.880, 95% CI 0.79-0.96; UC: AUROC = 0.938, 95% CI 0.87-1.00). High OSM concentrations were associated with anti-TNF discontinuation and use of rescue steroids in CD and UC. High pre-treatment OSM concentrations identify IBD patients at-risk of anti-TNF non-response at 1-year as well as other deleterious clinical outcomes., (© 2022. The Author(s).)

The clinical features of SARS-CoV-2 infection range from asymptomatic to severe disease with life-threatening complications. Understanding the persistence of immune responses in asymptomatic individuals merit special attention because of their importance in controlling the spread of the infections. We here studied the antibody and T cell responses, and a wide range of inflammation markers, in 56 SARS-CoV-2 antibody-positive individuals, identified by a population screen after the first wave of SARS-CoV-2 infection. These, mostly asymptomatic individuals, were reanalyzed 7-8 months after their infection together with 115 age-matched seronegative controls. We found that 7-8 months after the infection their antibodies to SARS-CoV-2 Nucleocapsid (N) protein declined whereas we found no decrease in the antibodies to Spike receptor-binding domain (S-RBD) when compared to the findings at seropositivity identification. In contrast to antibodies to N protein, the antibodies to S-RBD correlated with the viral neutralization capacity and with CD4 + T cell responses as measured by antigen-specific upregulation of CD137 and CD69 markers. Unexpectedly we found the asymptomatic antibody-positive individuals to have increased serum levels of S100A12, TGF-alpha, IL18, and OSM, the markers of activated macrophages-monocytes, suggesting long-term persistent inflammatory effect associated with the viral infection in asymptomatic individuals. Our results support the evidence for the long-term persistence of the inflammation process and the need for post-infection clinical monitoring of SARS-CoV-2 infected asymptomatic individuals., Competing Interests: Author PN was employed by company SYNLAB Estonia. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tserel, Jõgi, Naaber, Maslovskaja, Häling, Salumets, Zusinaite, Soeorg, Lättekivi, Ingerainen, Soots, Toompere, Kaarna, Kisand, Lutsar and Peterson.)

Objective: Periodontitis has been independently associated to cardiovascular disease. However, the biological mechanisms underlying such association are still partially unknown. Thus, this study aimed to discover immunological clues accounting for the increased risk of myocardial infarction (MI) in patients having periodontitis., Methods: We included 100 patients with a first MI, 50 with and 50 without severe periodontitis, and 100 age-matched, sex-matched and area-matched controls from the Periodontitis and Its Relation to Coronary Artery Disease Study. Participants underwent comprehensive clinical and laboratory examinations 6-10 weeks after the MI and plasma expression of 92 inflammation-related markers was assessed through proximity extension assay., Results: Patients who had an MI displayed altered expression of CCL19, TNFRSF9 and LAP TGF-β1 in comparison with controls. TNFRSF9 correlated significantly with the amount of alveolar bone loss. MI patients with deep periodontal pockets showed increased white cell count and higher expression of FGF-21, HGF, OSM, CCL20 and IL-18R1 than patients without. White cell count correlated significantly with four of these proteins., Conclusions: Collectively, our results indicate molecular markers that could be responsible for the increased systemic inflammatory activity in patients with MI with periodontitis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Multiple cytokines have been implicated in aneurysmal subarachnoid hemorrhage (aSAH), but tumor necrosis factor superfamily 14 (LIGHT/TNFSF14) and oncostatin-M (OSM) have not been previously explored., Aims of the Study: The primary objective of this study was to examine the relationship between TNFSF14 and OSM levels and survival. Our secondary goal was to investigate a potential association between these markers and the incidence of delayed cerebral ischemia (DCI)., Materials & Methods: We consecutively recruited 60 patients with a clinical diagnosis of aSAH. LIGHT/TNFSF14 and OSM serum concentrations were determined by ELISA. The primary endpoint was survival at Day 30, while development of DCI was assessed as secondary outcome., Results: Patients had significantly higher levels of both markers than the control group (median of LIGHT: 18.1 pg/ml vs. 7 pg/ml; p = 0.01; median of OSM: 10.3 pg/ml vs. 2.8 pg/ml, p < 0.001). Significantly lower serum level of LIGHT/TNFSF14 was found in nonsurviving patients (n = 9) compared with survivors (n = 51; p = 0.011). Based on ROC analysis, serum LIGHT/TNFSF14 with a cutoff value of >7.95 pg/ml predicted 30-day survival with a sensitivity of 71% and specificity of 78% (Area: 0.763; 95% CI: 0.604-0.921, p = 0.013). In addition, it was also a predictor of DCI with a sensitivity of 72.7% and a specificity of 62.5% (AUC: 0.702; 95% CI: 0.555-0.849, p = 0.018). Based on binary logistic regression analysis, LIGHT/TNFSF14 was found to be independently associated with 30-day mortality, but not with DCI., Conclusion: In this cohort, a higher serum level of LIGHT/TNFSF14 was associated with increased survival of patients with aSAH., (© 2021 The Authors. Acta Neurologica Scandinavica published by John Wiley & Sons Ltd.)

Background: Cytokines emerge as possible biomarkers of response in Crohn's disease (CD). We aimed to determine the plasmatic cytokine profiles of active CD patients who started infliximab (IFX) treatment and their capacity to predict the response to IFX., Methods: A total of 30 active CD patients receiving an induction therapy of IFX were enrolled in the study. Peripheral blood samples pretreatment were collected. Concentrations of 15 cytokines were measured by Luminex technology. Responses to IFX were evaluated by the drop in fecal calprotectin based on its logarithm-transformed values. A random forest (RF) predictive model was used for data analyses., Results: Samples of 22 patients were analyzed. The RF model ranked the following cytokines as the top predictors of the response: tumor necrosis factor alpha (TNFα), interleukin (IL)-13, oncostatin M (OSM), and IL-7 (p < 0.005). Partial dependency plots showed that high levels of IL-13 pretreatment, low TNFα levels, and low IL-7 levels were associated with a favorable IFX response. Increased levels of OSM and TNFα predicted unfavorable responses to IFX., Conclusions: We here show that a log drop in calprotectin strongly correlates with clinical parameters and it can be proposed as a useful objective clinical response predictor. Plasma TNFα, IL-13, Il-7, and OSM network could predict CD response to IFX before induction therapy, as assessed by calprotectin log drop., (© 2020 S. Karger AG, Basel.)

Background and Aims: Regenerating islet-derived protein 3-beta (Reg3β) and oncostatin-M (OSM), an inducer of Reg3β, are important for the recruitment of macrophages, tissue repair and survival after myocardial infarction. The study was planned to elucidate the diagnostic utility of serum Reg3β and OSM levels for the acute coronary syndrome (ACS)., Methods: Forty-two type 2 diabetes mellitus (T2DM) patients with ACS as cases and forty-two T2DM patients as controls were recruited. Routine biochemical investigations, creatine kinase-total (CK-T), and creatine kinase-MB (CK-MB) levels were estimated. Serum Reg3β and OSM levels were analysed by enzyme-linked immunosorbent assay., Results: Serum Reg3β and OSM levels were significantly higher in cases as compared to controls. Serum Reg3β and OSM levels were positively correlated with random blood glucose, serum CK-total, CK-MB levels, and negatively correlated with serum high-density lipoprotein cholesterol (HDL-C) levels. Receiver operating characteristics curve analysis showed that serum OSM and Reg3β levels can be used for the diagnosis of ACS in patients with T2DM as compared to CK-MB levels. On regression analysis, serum Reg3β level was positively associated with body mass index and negatively with serum HDL-C levels and serum OSM level was positively associated with waist circumference and random blood glucose and negatively with serum HDL-C levels., Conclusion: Serum Reg3β and OSM levels may be used as complementary markers besides traditional cardiac markers for the diagnosis of ACS in patients with T2DM. However, further studies are still needed to verify our claim., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest related to this article., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Oncostatin M is upregulated in Crohn's disease inflamed intestinal mucosa, and has been suggested as a promising biomarker to predict responsiveness to anti-TNF therapy in patients with inflammatory bowel diseases., Aim: To evaluate the suitability of serum oncostatin M as a predictive marker of response to infliximab in Crohn's disease., Methods: We included patients treated with infliximab monotherapy. All patients underwent colonoscopy at week 54 to evaluate mucosal healing. Serum oncostatin M and faecal calprotectin were measured at baseline and after 14 weeks of treatment. Mann-Whitney test was used to evaluate correlation of oncostatin M and faecal calprotectin at baseline and week 14 with mucosal healing at week 54. Their accuracy in predicting mucosal healing was assessed by area under the curve (AUC)., Results: In a cohort of 45 included patients, 27 displayed mucosal healing. At both baseline and week 14, oncostatin M levels were significantly lower in patients with mucosal healing than in patients not achieving this endpoint (P < 0.001). Faecal calprotectin levels at week 14 were lower also in responders than nonresponders (P < 0.001). Oncostatin M values at baseline and week 14 were significantly associated (Spearman correlation = 0.92, P < 0.001). The diagnostic accuracy of oncostatin M at baseline in predicting mucosal healing (AUC = 0.91) was greater than faecal calprotectin (AUC = 0.51, P < 0.001)., Conclusion: These results suggest that oncostatin M can predict the outcome of infliximab treatment. Compared with faecal calprotectin, the predictive capability of oncostatin M was appreciable at baseline, thus indicating oncostatin M as a promising biomarker for driving therapeutic choices in Crohn's disease., (© 2020 John Wiley & Sons Ltd.)

Background: Oncostatin M (OSM) is a pleiotropic cytokine of the interleukin-6 family. The role of OSM in sepsis remains unknown., Methods: Serum OSM level was determined and analyzed in septic patients on the day of intensive care unit (ICU) admission. Furthermore, the effects of OSM on polymicrobial sepsis induced by cecal ligation and puncture (CLP) were assessed., Results: On the day of ICU admission, septic patients had significantly higher serum OSM levels when compared with ICU patient controls and healthy volunteers, which were related to the severity of sepsis, including parameters such as the sequential (sepsis-related) organ failure assessment score, procalcitonin level, and white blood cell number. A high serum OSM level on ICU admission was associated with 28-day mortality in septic patients. In CLP-induced polymicrobial sepsis, anti-OSM antibody decreased tissue inflammation and injury, and thus improved survival, while local and systemic bacterial dissemination was almost constant. Complementarily, supplementation with recombinant OSM protein in septic mice increased tissue injury, amplified inflammation, and worsened mortality after CLP, while it did not affect bacterial dissemination in septic mice., Conclusions: Sepsis results in an increased production of OSM, which might be a potential prognostic biomarker and therapeutic target for sepsis., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective Activated macrophages (M1-type macrophages) in adipose tissue secrete many proinflammatory cytokines that induce insulin resistance (IR). Oncostatin M (OSM), a member of the interleukin-6 (IL-6) family of Gp130 cytokines, plays an important role in a variety of biological functions, including the regulation of inflammatory responses. Proinflammatory cytokines released in patients with IR trigger a chronic, low-grade inflammatory reaction in blood vessel walls. This inflammator response leads to endothelial damage, which is the main mechanism for atherosclerosis and many cardiovascular diseases. Animal studies have reported a relationship between OSM and IR. To the best of our knowledge, however, few clinical studies have examined this topic. Therefore, we studied the relationship between serum levels of OSM and IR. Subjects and methods This prospective cross-sectional case-control study enrolled 50 people with IR (according to the HOMA-IR and QUICKI indices) and 34 healthy controls. The fasting blood concentrations of insulin, glucose, blood urea nitrogen (BUN), creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, total cholesterol, C-reactive protein (CRP), and OSM were determined. Results There were no significant differences between the two groups in age, sex, and HbA1c levels. Univariate analyses showed that waist circumference (WC) and levels of fasting glucose, insulin, CRP, HDL-C, OSM, HOMA-IR, and QUICKI differed between the two study groups. In multivariate analyses, both IR indices (QUICKI and HOMA) and OSM differed between the two groups. Conclusion OSM was correlated with the IR indices (QUICKI and HOMA). For simplicity, it might replace the other IR indices in the future. Further detailed studies are needed to confirm this.

An increasing body of evidence suggests that age-related immune changes and chronic inflammation contribute to cancer development. Recognizing that exercise has protective effects against cancer, promotes immune function, and beneficially modulates inflammation with ageing, this review outlines the current evidence indicating an emerging role for exercise immunology in preventing and treating cancer in older adults. A specific focus is on data suggesting that muscle- derived cytokines (myokines) mediate anti-cancer effects through promoting immunosurveillance against tumourigenesis or inhibiting cancer cell viability. Previous studies suggested that the exercise-induced release of myokines and other endocrine factors into the blood increases the capacity of blood serum to inhibit cancer cell growth in vitro. However, little is known about whether this effect is influenced by ageing. Prostate cancer is the second most common cancer in men. We therefore examined the effects of serum collected before and after exercise from healthy young and older men on the metabolic activity of androgen-responsive LNCaP and androgen-unresponsive PC3 prostate cancer cells. Exercise-conditioned serum collected from the young group did not alter cell metabolic activity, whereas post-exercise serum (compared with pre-exercise serum) from the older men inhibited the metabolic activity of LNCaP cancer cells. Serum levels of candidate cancer-inhibitory myokines oncostatin M and osteonectin increased in both age groups following exercise. Serum testosterone increased only in the younger men postexercise, potentially attenuating inhibitory effects of myokines on the LNCaP cell viability. The data from our study and the evidence in this review suggest that mobilizing serum factors and immune cells may be a key mechanism of how exercise counteracts cancer in the older population., (Copyright © 2020 International Society of Exercise and Immunology. All rights reserved.)

Objective: Previous studies indicate a role for Oncostatin M (OSM) in atherosclerosis and other chronic inflammatory diseases for which inhibitory antibodies are in development. However, to date no intervention studies with OSM have been performed, and its relation to coronary heart disease (CHD) has not been studied., Approach and Results: Gene expression analysis on human normal arteries (n = 10) and late stage/advanced carotid atherosclerotic arteries (n = 127) and in situ hybridization on early human plaques (n = 9) showed that OSM, and its receptors, OSM receptor (OSMR) and Leukemia Inhibitory Factor Receptor (LIFR) are expressed in normal arteries and atherosclerotic plaques. Chronic OSM administration in APOE*3Leiden.CETP mice (n = 15/group) increased plasma E-selectin levels and monocyte adhesion to the activated endothelium independently of cholesterol but reduced the amount of inflammatory Ly-6CHigh monocytes and atherosclerotic lesion size and severity. Using aptamer-based proteomics profiling assays high circulating OSM levels were shown to correlate with post incident CHD survival probability in the AGES-Reykjavik study (n = 5457)., Conclusions: Chronic OSM administration in APOE*3Leiden.CETP mice reduced atherosclerosis development. In line, higher serum OSM levels were correlated with improved post incident CHD survival probability in patients, suggesting a protective cardiovascular effect., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: Danielle van Keulen and Dennie Tempel are employed by Quorics B.V., Maarten D Sollewijn Gelpke by Molecular Profiling Consulting, Lori L Jennings by Novartis and Kim Holmstrøm and Boye Schnack Nielsen PhD by Bioneer A/S. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials,as detailed online in the guide for authors.

Bariatric surgery is currently the most effective therapy for type 2 diabetes. However, the mechanisms underlying its beneficial effects remain elusive. Here we studied the effects of bariatric surgery on circulating meteorin-like (Metrnl) and oncostatin m (OSM) levels, two hormones intimately linked to energy homeostasis. Metrnl and OSM levels were assessed at baseline, 6 and 12 months after laparoscopic sleeve gastrectomy (LSG) in 25 patients with obesity, as well as in 33 normal-weight controls. At baseline, patients with obesity showed lower Metrnl and higher OSM levels compared to controls. LSG increased Metrnl and decreased OSM levels, in correlation to improvements in glucose and lipid homeostasis. Our data indicate that LSG conversely modulated Metrnl and OSM levels, and suggest that a dual approach modulating these two molecules might provide a novel strategy for obesity and type 2 diabetes treatment.

Aim: Oncostatin M (OSM) is an inflammatory cytokine of the gp130 family. OSM could participate in adverse cardiovascular remodeling through regulation of FGF23., Materials & Methods: OSM levels were determined in 80 heart failure patients with reduced left ventricular ejection fraction (HFrEF)., Results: OSM levels are significantly increased in HFrEF patients compared with healthy subjects. We have also demonstrated that, in HFrEF patients, plasma OSM levels are correlated to parathyroid hormone PTH(1-84) and 1,25(OH) 2 D, two other biomarkers related to bone and mineral metabolism and associated to adverse cardiovascular outcomes., Conclusion: OSM concentrations are elevated in HFrEF patients and could interplay with parathyroid hormone and vitamin D impacting cardiovascular function. Nevertheless, the prognostic value of OSM testing appears limited.

Background: Preclinical and epidemiologic studies suggest that garlic intake is inversely associated with the progression of cancer and cardiovascular disease., Objective: We designed a study to probe the mechanisms of garlic action in humans., Methods: We conducted a randomized crossover feeding trial in which 17 volunteers consumed a garlic-containing meal (100 g white bread, 15 g butter, and 5 g raw, crushed garlic) or a garlic-free control meal (100 g white bread and 15 g butter) after 10 d of consuming a controlled, garlic-free diet. Blood was collected before and 3 h after test meal consumption for gene expression analysis in whole blood. Illumina BeadArray was used to screen for genes of interest, followed by real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) on selected genes. To augment human study findings, Mono Mac 6 cells were treated with a purified garlic extract (0.5 μL/mL), and mRNA was measured by qRT-PCR at 0, 3, 6, and 24 h., Results: The following 7 genes were found to be upregulated by garlic intake: aryl hydrocarbon receptor (AHR), aryl hydrocarbon receptor nuclear translocator (ARNT), hypoxia-inducible factor 1α (HIF1A), proto-oncogene c-Jun (JUN), nuclear factor of activated T cells (NFAT) activating protein with immunoreceptor tyrosine-based activation motif 1 (NFAM1), oncostatin M (OSM), and V-rel avian reticuloendotheliosis viral oncogene homolog (REL). Fold-increases in mRNA transcripts ranged from 1.6 (HIF1A) to 3.0 (NFAM1) (P < 0.05). The mRNA levels of 5 of the 7 genes that were upregulated in the human trial were also upregulated in cell culture at 3 and 6 h: AHR, HIF1A, JUN, OSM, and REL. Fold-increases in mRNA transcripts in cell culture ranged from 1.7 (HIF1A) to 12.1 (JUN) (P < 0.01). OSM protein was measured by ELISA and was significantly higher than the control at 3, 6, and 24 h (24 h: 19.5 ± 1.4 and 74.8 ± 1.4 pg/mL for control and garlic, respectively). OSM is a pleiotropic cytokine that inhibits several tumor cell lines in culture., Conclusion: These data indicate that the bioactivity of garlic is multifaceted and includes activation of genes related to immunity, apoptosis, and xenobiotic metabolism in humans and Mono Mac 6 cells. This trial is registered at clinicaltrials.gov as NCT01293591., (© 2015 American Society for Nutrition.)

Background: Oncostatin M (OSM) is an inflammatory cytokine which has been found to be expressed at sites of atherosclerotic lesions. We sought to investigate whether serum OSM levels are associated with coronary stenosis in patients with coronary artery disease (CAD)., Methods: A total of 117 patients with CAD and 35 patients without CAD who underwent coronary angiography were enrolled in this study. Serum levels of OSM were measured by enzyme-linked immunosorbent assay. The severity of CAD was assessed by the number of diseased vessels and coronary stenosis score., Results: Serum OSM levels were significantly elevated in CAD patients compared with those without CAD. A stepwise increase in serum levels of OSM was also found depending on the number of > 50% coronary stenosis: median value 4.24 pg/mL (2.72 - 4.24) in 1-vessel disease, 6.44 pg/mL (4.87 - 10.09) in 2-vessel disease, and 7.83 pg/mL (5.41 - 10.37) in 3-vessel disease (p = 0.007 for trend). Correlation analysis showed coronary stenosis score positively correlated with age (r = 0.202, p = 0.029), current smoking (r = 0.210, p = 0.023), hypertension (r = 0.256, p = 0.005), TG (r = 0.408, p = 0.000), LDL-cholesterol (r = 0.325, p < 0.001), and hs-CRP (r = 0.307, p = 0.001), and correlated with OSM (r = 0.314, p < 0.001)., Conclusions: Our data suggest that increased serum OSM levels are associated with the coronary stenosis score and that circulating levels of this chemokine may reflect the extent of coronary atherosclerosis.

Objective: The aim of this study was to evaluate preoperative serum oncostatin M (OSM) concentration as a diagnostic marker in colon cancer patients and its association with clinicopathologic variables., Patients and Methods: Preoperative serum OSM concentrations were measured in 100 colon cancer patients and 70 healthy volunteers by enzyme-linked immunosorbent assay (ELISA)., Results: Serum OSM concentrations were significantly higher in colon cancer patients than in controls (p < 0.001). Serum OSM concentrations increased significantly with higher T stage (p < 0.001) and were significantly higher in patients with increased tumor burden, lymphovascular involvement, and lymph node and distant metastasis (p < 0.001 for each)., Conclusions: To our knowledge, this is the first report showing that elevated OSM concentration was associated with colon cancer and its clinicopathologic variables, including invasion and metastasis. These findings indicate that serum OSM may serve as a novel biomarker in the diagnosis of colon cancer.

Introduction: Oncostatin M (OSM) has been implicated in the pathophysiology of rheumatoid arthritis (RA) through its effect on inflammation and joint damage. GSK315234 is a humanised anti-OSM Immunoglobulin G1 (IgG1) monoclonal antibody (mAb). This 3-part study examines the safety, tolerability and efficacy of GSK315234 in patients with active RA., Method: This was a 3-part (Parts A, B and C), multicenter study. Part A and Part B were randomised, double-blind, placebo-controlled, Bayesian adaptive dose finding studies to investigate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of single (Part A) and 3 repeat (Part B) intravenous infusions of GSK315234 in patients with active RA on a background of methotrexate (MTX). Part C was a single dose, randomised, single-blind, placebo-controlled study to assess subcutaneously administered GSK315234 to patients with active RA on a background of MTX., Result: The primary endpoint of the study was mean change in DAS28 at Day 28 in Part A and Day 56 in Part B and C. All patients receiving at least one dose of GSK315234 were included in safety analysis. In Part A, there were statistically significant differences in DAS28 between 3 mg/kg and placebo at Day 56, 84 and 91. There was also a statistically significant difference in DAS28 between 0.3 mg/kg, 3 mg/kg and 10 mg/kg, as compared to placebo, at Day 84. Although these changes were small and occurred late, they supported progression to Part B and C to determine the therapeutic potential of GSK315234. For Part B, no significant difference was observed between 6 mg/kg and placebo. For Part C, a statistically significant difference in DAS28 was observed at Day 40, Day 84 and Day 100 between the 500 mg subcutaneous group, as compared to placebo. No significant findings were observed at any of the time points for EULAR response criteria, ACR20, ACR50 or ACR70. An exploratory analysis of clinical, pharmacokinetic and pharmacodynamics data suggests the lack of efficacy may be due to moderate binding affinity and rapid off-rate of GSK315234 as compared to the higher affinity OSM receptor causing a protein carrier effect prolonging the half life of OSM due to accumulation of the OSM/antibody complex in the serum and synovial fluid., Conclusion: Our data highlighted the importance of binding affinity and off-rate effect of a mAb to fully neutralize the target and how this may influence its efficacy and potentially worsen disease activity. Using an anti-OSM mAb with high affinity should test this hypothesis and examine the potential of OSM as a therapeutic target in RA., Trial Registration: ClinicalTrials.gov no: NCT00674635.

Background: The aim of the present study is to investigate gingival crevicular fluid (GCF) and plasma acute-phase cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-11 (IL-11), oncostatin M (OSM), and leukemia inhibitory factor (LIF) levels in patients with different periodontal diseases., Methods: Eighty individuals were included in this study; 20 with chronic periodontitis (CP), 20 with generalized aggressive periodontitis (GAgP), 20 with gingivitis, and 20 classified as healthy (H). Probing depth, clinical attachment level, plaque index, and papilla bleeding index were recorded. Plasma and GCF IL-1β, IL-6, IL-11, OSM, and LIF levels were analyzed by enzyme-linked immunosorbent assay., Results: CP and GAgP groups had significantly higher GCF IL-1β, IL-6, and IL-11 levels when compared with the H group (P <0.05). Conversely, GCF LIF levels of the CP and GAgP groups were lower than those of the H group (P <0.05). GCF OSM levels did not differ significantly among study groups. Plasma levels of all the cytokines studied were not significantly different among the study groups., Conclusions: Based on the present data, elevated IL-1β, IL-6, and IL-11 GCF levels, but not plasma levels, are suggested as reliable inflammatory biomarkers in periodontal diseases. Decreased LIF levels in diseased groups might reflect the possible beneficial effects of LIF in the modulation of inflammatory response in gingiva.

The JAK2 mutation V617F is detectable in a majority of patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs). Enforced expression of JAK2 V617F in mice induces myeloproliferation and bone marrow (BM) fibrosis, suggesting a causal role for the JAK2 mutant in the pathogenesis of MPNs. However, little is known about mechanisms and effector molecules contributing to JAK2 V617F-induced myeloproliferation and fibrosis. We show that JAK2 V617F promotes expression of oncostatin M (OSM) in neoplastic myeloid cells. Correspondingly, OSM mRNA levels were increased in the BM of patients with MPNs (median 287% of ABL, range 22-1450%) compared to control patients (median 59% of ABL, range 12-264%; P < 0.0001). OSM secreted by JAK2 V617F+ cells stimulated growth of fibroblasts and microvascular endothelial cells and induced the production of angiogenic and profibrogenic cytokines (HGF, VEGF, and SDF-1) in BM fibroblasts. All effects of MPN cell-derived OSM were blocked by a neutralizing anti-OSM antibody, whereas the production of OSM in MPN cells was suppressed by a pharmacologic JAK2 inhibitor or RNAi-mediated knockdown of JAK2. In summary, JAK2 V617F-mediated up-regulation of OSM may contribute to fibrosis, neoangiogenesis, and the cytokine storm observed in MPNs, suggesting that OSM might serve as a novel therapeutic target molecule in these neoplasms.

The Golgi phosphoprotein GP73 is elevated in the circulation of individuals with a diagnosis of hepatocellular carcinoma. Its usefulness as a biomarker of HCC is questioned, since it has also been reported to be elevated in the circulation of people with liver cirrhosis. Regulation of GP73 by inflammatory cytokines is therefore of interest. The interleukin-6 (IL-6) family cytokines were tested for effects on GP73 mRNA and/or protein levels in human hepatoblastoma HepG2 cells. Levels of GP73 mRNA and protein were up-regulated in HepG2 cells following treatment with either proinflammatory cytokine IL-6 or the related cytokine oncostatin M (OSM). Induction required the shared receptor subunit gp130, and correlated with increased tyrosine phosphorylation of STAT3. Maximal cytokine-mediated induction was not observed in the presence of protein synthesis inhibitor cycloheximide, suggesting additional regulatory factors play an important role. ELISA measurement of GP73 and IL-6 levels in the sera of patients with pre-malignant liver disease revealed a significant correlation between circulating levels of the two proteins. Similarly, a sensitive ELISA assay was developed to measure circulating OSM. OSM levels were elevated 6-7 fold in sera from patients with either cirrhosis or HCC relative to controls without liver disease. Although there was an association between levels of GP73 and OSM in serum from people with liver cirrhosis, there was not a statistically significant correlation in HCC, suggesting that the role of the cytokines in determining circulating levels may be complex. To our knowledge, this is the first report of OSM elevation being associated with liver disease.

Background: Intrinsic asthma, etiology unknown, occurs later in life, mostly in females. It is associated with nasal polyps and massive eosinopillic infiltration of the respiratory mucous membrane, aspirin intolerance and steroid dependence. The aim of the study was to determine the cytokine and chemokine profile in sera of intrinsic asthmatics and control subjects., Methods: Blood was taken from 10 intrinsic asthmatic female and 12 control female subjects. Expression profile of 42 different cytokines and chemokines were measured using a microarray composed of antibodies against the cytokines and chemokines. Complete blood count and C-reactive protein were measured, to assess the state of inflammation in both groups., Results: We have identified Macrophage Colony Stimulating Factor, a proinflammatory cytokine and Monocyte Chemoattractant Protein 2, a CC chemokine as having significantly higher expression levels in intrinsic asthmatic subjects compared to controls (341.71±31.28 SEM Signal intensity) versus (247.97±28.09 SEM Signal intensity), p=0.036 and (397.07±38.19 SEM Signal intensity) versus (311.33±28.76 SEM Signal intensity), p=0.036, respectively. There were no significant differences in the other cytokines and chemokines measured nor were there any differences in the inflammatory measurements between the two groups except for eosinophil counts, the hall mark of intrinsic asthma., Conclusion: Macrophage Colony Stimulating Factor and Monocyte Chemoattractant Protein are elevated in sera of intrinsic asthmatics compared to normal controls. These cytokines may have a critical role in the inflammatory pathology of intrinsic asthma., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Background/aim: Oncostatin M (OSM) and interleukin-6 (IL-6) are growth factors for prostate cancer (PC). Vascular endothelial growth factor (VEGF) and urokinase-type plasminogen-activator (u-PA) have been implicated in tumour progression. A possible interaction between IL-6, OSM, u-PA and VEGF in PC was investigated., Materials and Methods: Primary prostate epithelial cells (PPEC) and DU-145 PC cells were treated with IL-6 or OSM and the effects on u-PA and VEGF expression were studied. Plasma levels of IL-6, OSM, u-PA and VEGF were determined in patients with or without PC., Results: In DU-145 cells, OSM and IL-6 up-regulated u-PA and VEGF significantly. Higher levels of IL-6 and OSM in metastasising PC than in nonmetastasising PC and benign prostatic hyperplasia (BPH) and correlations between IL-6, OSM, u-PA and VEGF were found., Conclusion: OSM and IL-6 increase u-PA and VEGF in DU-145 cells but not in PPEC and possibly, by promoting matrix degradation and angiogenesis, could play a role in the pathogenesis of prostate cancer.

Aim: The aim of this study was to measure the level of Oncostatin M (OSM) a gp130 cytokine in the gingival crevicular fluid (GCF) and serum of chronic periodontitis patients and to find any correlation between them before and after periodontal therapy (scaling and root planing, SRP)., Methodology: 60 subjects (age 25-50 years) were enrolled into three groups (n=20 per group), group I (healthy), group II (gingivitis) and group III (chronic periodontitis). Group III subjects were followed for 6-8 weeks after the initial periodontal therapy (SRP) as the group IV (after periodontal therapy). Clinical parameters were assessed as gingival index (GI), probing depth (PD), clinical attachment level (CAL), and radiographic evidence of bone loss. GCF and serum levels of OSM were measured by using Enzyme Linked Immunosorbent Assay (ELISA)., Results: It was found that mean OSM levels had been elevated in both the GCF and serum of chronic periodontitis subjects (726.65 +/- 283.56 and 65.59 +/- 12.37 pg mL(-1), respectively) and these levels were decreased proportionally after the periodontal therapy (95.50 +/- 38.85 and 39.98 +/- 16.69 pg mL(-1) respectively). However, OSM was detected in GCF of healthy subjects (66.15 +/- 28.10 pg mL(-1)) and gingivitis-suffering subjects (128.33 +/- 22.96 pg mL(-1)) and was found as below the detectable limit (approximately equal 0.0 pg mL(-1)) in the serum of same subjects. Significant correlation has been found between clinical parameters and GCF-serum levels of OSM., Conclusion: Increased OSM level both in the GCF and serum, and the decreased levels after initial periodontal therapy (SRP) may suggest a use as an inflammatory biomarker in the periodontal disease.

Objective: Periodontitis is considered to be a risk factor for systemic diseases such as atherosclerosis, diabetes, etc., and cytokines play a key role. The present study was carried out to measure the level of serum oncostatin M (OSM) in patients with chronic periodontitis, and to evaluate the effect of non-surgical periodontal therapy on the serum OSM concentration., Materials and Methods: Sixty subjects were divided into three groups (each group n = 20) based on the gingival index (GI), probing pocket depth (PPD) and clinical attachment level (CAL): group I healthy; group II gingivitis; and group III chronic periodontitis. Group III patients were followed for 8 weeks after non-surgical periodontal therapy as the after-treatment group (group IV). Estimation of serum OSM was done using an enzyme-linked immunosorbent assay., Results: The mean OSM concentrations in serum were highest in the chronic periodontitis group (mean 68.05 pg ml(-1)) and decreased following treatment (39.65 pg ml(-1)) while OSM was undetectable in healthy subjects or in patients with gingivitis., Conclusion: Increased serum OSM concentration in patients with chronic periodontitis and its positive correlation with PPD and CAL, suggest its role as an inflammatory biomarker in periodontal disease and it may exaggerate other systemic conditions such as atherosclerosis and rheumatoid arthritis.

Oncostatin M, a unique member of the interleukin (IL)-6 cytokine family, is thought to be involved in airway remodeling. The expression of oncostatin M in the lower airways is unknown. The aim of this study was to measure the sputum expression of oncostatin M in patients with asthma with and without irreversible airflow obstruction. Induced sputum was collected from nonsmoking adults with stable asthma (n = 53), 31 with incomplete reversibility of airflow obstruction. Peripheral blood cells were isolated and stimulated with lipopolysaccharide in 10 participants with asthma and irreversible airflow obstruction. Oncostatin M protein levels were determined in supernatant, whereas RNA was extracted to determine Oncostatin M mRNA expression using real-time polymerase chain reaction (PCR). Oncostatin M mRNA expression and protein levels were significantly higher in the sputum of asthmatics with irreversible airflow obstruction. Sputum oncostatin M levels were highest in people with severe airflow obstruction and were localized to airway neutrophils and macrophages. Peripheral blood neutrophils released more oncostatin M when stimulated with lipopolysaccharide compared with unstimulated neutrophils. Sputum oncostatin M is increased in asthma with irreversible airflow obstruction and is present in airway neutrophils and macrophages. Oncostatin M may link airway inflammation to remodeling in asthma.

Objectives: Oncostatin M (OSM), hepatocyte growth factor (HGF) and soluble glycoprotein 130 (sgp130) have been demonstrated to be involved in fetal liver development. In this study, we examined the relation between neonatal jaundice and OSM, gp130 or HGF levels in umbilical cord blood., Design: A cross-sectional study of 160 neonates born at Okayama University Hospital., Setting: Tertiary referral center serving a population of three million., Methods: The serum concentrations of OSM, HGF and sgp130 in umbilical venous cord blood were measured and compared with the clinical records of these neonates., Results: The HGF level was correlated to both gestational week (p=0.007) and birthweight (p=0.015), as well as to total bilirubin on Day 1 (p=0.032). In preterm neonates, the HGF levels were lower in neonates who received phototherapy (photo group) than in those who did not receive phototherapy (non-photo group) (p=0.002). In contrast, in term neonates, OSM levels were lower in the photo group than in the non-photo group (p=0.0003)., Conclusions: These findings suggest that the phototherapy requirement for neonatal jaundice may be associated with lower umbilical HGF concentration in preterm neonates and with lower umbilical OSM concentration in term neonates.