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Bjorn M.E.,Roskilde Hospital | Bjorn M.E.,Institute for Inflammation Research | Hasselbalch H.C.,Roskilde Hospital
Mediators of Inflammation | Year: 2015

Reactive oxygen species (ROS) have been implicated in a wide variety of disorders ranging between traumatic, infectious, inflammatory, and malignant diseases. ROS are involved in inflammation-induced oxidative damage to cellular components including regulatory proteins and DNA. Furthermore, ROS have a major role in carcinogenesis and disease progression in the myeloproliferative neoplasms (MPNs), where the malignant clone itself produces excess of ROS thereby creating a vicious self-perpetuating circle in which ROS activate proinflammatory pathways (NF-κB) which in turn create more ROS. Targeting ROS may be a therapeutic option, which could possibly prevent genomic instability and ultimately myelofibrotic and leukemic transformation. In regard to the potent efficacy of the ROS-scavenger N-acetyl-cysteine (NAC) in decreasing ROS levels, it is intriguing to consider if NAC treatment might benefit patients with MPN. The encouraging results from studies in cystic fibrosis, systemic lupus erythematosus, and chronic obstructive pulmonary disease warrant such studies. In addition, the antioxidative potential of the widely used agents, interferon-alpha2, statins, and JAK inhibitors, should be investigated as well. A combinatorial approach using old agents with anticancer properties together with novel JAK1/2 inhibitors may open a new era for patients with MPNs, the outlook not only being "minimal residual disease" and potential cure but also a marked improvement in inflammation-mediated comorbidities. © 2015 Mads Emil Bjørn and Hans Carl Hasselbalch. Source

Andersen L.B.,University of Southern Denmark | Andersen L.B.,Norwegian School of Sport Sciences | Muller K.,Paediatric Clinic II | Eiberg S.,Team Denmark | And 5 more authors.
Metabolism: Clinical and Experimental | Year: 2010

The aim was to evaluate the possible role of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), C-reactive protein (CRP), low fitness, and fatness in the early development of clustering of cardiovascular disease (CVD) risk factors and insulin resistance. Subjects for this cross-sectional study were obtained from 18 schools near Copenhagen, Denmark. Two hundred ten 9-year-old children were selected for cytokine analysis from 434 third-grade children with complete CVD risk profiles. The subgroup was selected according to the CVD risk factor profile (upper and lower quartile of a composite CVD risk score). All the CVD risk factors and CRP differed between the high- and low-risk groups; but plasma glucose, TNF-α, and IL-6 had small and inconsistent differences. Strong associations were found between CVD risk scores and fitness (VO2peak) or fatness. No associations were found between CVD risk scores and TNF-α and IL-6. C-reactive protein was associated with fitness, fatness, and CVD risk score. This study does not support an association between plasma IL-6 or TNF-α and low insulin sensitivity or clustering of CVD risk factors in a young cohort. Inflammation was more pronounced in fat and unfit children based on the association with CRP levels. The association between fitness and fatness variables, insulin resistance, and clustered risk could be caused by other mechanisms related to these exposures. The role of IL-6 remains unclear. © 2010 Elsevier Inc. Source

Bugge A.,University of Southern Denmark | El-Naaman B.,University of Southern Denmark | G. McMurray R.,University of North Carolina at Chapel Hill | Froberg K.,University of Southern Denmark | And 4 more authors.
Experimental Diabetes Research | Year: 2012

The purpose of this study was to determine whether levels of interleukin-6 (IL-6) in childhood are related to insulin resistance in adolescence. Further, to explore how fatness and cardiorespiratory fitness (VO 2peak) moderate this relationship. Methods. 292 nine-year-old children (n = 292) were followed for 4 years. Anthropometrics and VO 2peak were measured. Fasting blood samples were analyzed for IL-6, insulin, and glucose. Homeostasis model assessment (HOMA-IR) was used as a measure of insulin resistance. Results. For girls but not boys, levels of IL-6 at age 9yrs correlated with HOMA-IR at age 13yrs: r = 0.223, P = 0.008. Girls with IL-6 levels within the highest quartile at age 9yrs had an odds ratio of 3.68 (CI = 1.588.57) being in the highest quartile of HOMA-IR four years later. Conclusion. In this cohort, IL-6 levels in childhood were related to insulin resistance in adolescence, but only for girls. Copyright © 2012 Anna Bugge et al. Source

Steenholdt C.,Herlev Hospital | Bendtzen K.,Institute for Inflammation Research | Brynskov J.,Herlev Hospital | Thomsen O.O.,Herlev Hospital | Ainsworth M.A.,Herlev Hospital
American Journal of Gastroenterology | Year: 2014

OBJECTIVES:Cost-effective guidance of therapeutic strategy in Crohn's disease patients with secondary infliximab (IFX) treatment failure may be achieved by serum IFX and anti-IFX antibody (Ab) measurements by radioimmunoassay (RIA). This study investigated implications of using other techniques for this purpose.METHODS:This is a post hoc analysis of randomized clinical trial including 66 Crohn's disease patients with IFX failure in whom IFX and anti-IFX Ab measurements by RIA had been used for therapeutic guidance. Samples were additionally assessed by enzyme-linked immunosorbent assay (ELISA), homogeneous mobility shift assay (HMSA), and functional cell-based reporter gene assay (RGA).RESULTS:IFX detection was comparable between assays (82% RIA, 76% ELISA, 88% HMSA, and 74% RGA), and it correlated significantly (Pearson's r=0.91-0.97, P<0.0001). However, IFX concentrations varied systematically between all pair of assays except RIA-RGA. Anti-IFX Ab detection was variable (27% RIA, 9% ELISA, 33% HMSA, and 11% RGA), but correlated significantly (Pearson's r=0.77-0.96; P<0.0001). Anti-IFX Abs detected by RIA and HMSA were often from sera without drug-neutralizing activity (RGA). Assays agreed on classification of underlying mechanism for treatment failure in most cases (79-94%). The majority (74-88%) failed IFX owing to pharmacodynamic problems, or had noninflammatory pathophysiology for symptoms resembling relapse. Applied threshold for therapeutic vs. subtherapeutic IFX level influenced classifications. The four different assays did not differ in terms of the ability to predict response to interventions defined by the algorithm. CONCLUSIONS:Despite variable analytical properties, common assays result in similar classifications and interventions in patients with IFX treatment failure, and with comparable clinical outcomes. Implications are, however, profound for the minority classified differently. © 2014 by the American College of Gastroenterology. Source

Mellgren K.,Queen Silvias Hospital for Children and Adolescents | Mellgren K.,Gothenburg University | Hedegaard C.J.,Institute for Inflammation Research | Schmiegelow K.,Copenhagen University | Muller K.,Institute for Inflammation Research
Journal of Pediatric Hematology/Oncology | Year: 2012

Non-Hodgkin lymphoma (NHL) has been associated with elevated levels of inflammatory and immune-regulating cytokines, and polymorphisms in the genes encoding interleukin (IL)-10 and tumor necrosis factor (TNF)-α have been associated with increased incidence of certain subtypes of NHL. The aim of the present study was to screen for a broader spectrum of growth factors and inflammatory mediators and to compare the profiles in different subtypes of NHL in pediatric patients. Serum samples were collected at diagnosis from 31 pediatric patients diagnosed with NHL admitted at Rigshospitalet, Copenhagen, between 1995 and 2008. Cytokines and growth factors were measured in serum using the Luminex platform by application of a 30-plex kit. Levels of IL-6, IL-2R, IL-10, TNF-RI, and macrophage inflammatory protein-1α were significantly higher in patients with anaplastic large-cell lymphoma compared with patients diagnosed with B-cell lymphomas and lymphoblastic lymphomas. High levels of IL-4, IL-13, TNF-RI, and epidermal growth factor were associated with a poorer general condition at diagnosis. The present study suggests that NHL subgrouping and the general condition of pediatric patients at diagnosis are associated with plasma levels of growth factors and inflammatory mediators at presentation. Copyright © 2012 by Lippincott Williams & Wilkins. Source

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