title: Tumor necrosis factor blockade differentially affects innate inflammatory and Th17 cytokines in rheumatoid arthritis.
abstract: OBJECTIVE
  To evaluate the effect of a tumor necrosis factor-α (TNF-α) inhibitor (etanercept) on innate inflammatory and Th17 cytokines in patients with rheumatoid arthritis (RA).
  
  
  METHODS
  Serum samples were collected from 40 patients with active RA refractory to conventional disease-modifying antirheumatic drugs who initiated therapy with etanercept plus methotrexate (MTX). Treatment response was assessed at Week 24 according to the European League Against Rheumatism response criteria. Serum levels of interleukin 6 (IL-6), TNF-α, IL-32, IL-23, IL-17A, IL-21, and IL-22 were measured in patients with RA and 25 healthy controls.
  
  
  RESULTS
  Patients with RA had increased levels of IL-6 (p < 0.001), IL-32 (p < 0.001), IL-23 (p < 0.001), and a trend toward increased IL-21 in the sera compared to controls. At 24 weeks' posttreatment, followup serum samples of etanercept responders had decreased levels of IL-6 (p < 0.001) and increased IL-21 (p < 0.05) and IL-32 (p < 0.001), while there were no differences in cytokine levels in non-responders. Serum IL-6 levels were positively correlated with levels of erythrocyte sedimentation rate (r = 0.458, p < 0.01), C-reactive protein (r = 0.593, p < 0.01), and 28-joint Disease Activity Score (r = 0.432, p < 0.01) at baseline. Serum IL-21 levels were positively correlated with levels of rheumatoid factor (r = 0.513, r = 0.633, both p < 0.01) and antimutated citrullinated vimentin antibodies (r = 0.515, p < 0.01; r = 0.428, p < 0.05) at baseline and after 24 weeks of treatment with etanercept.
  
  
  CONCLUSIONS
  Multiple inflammatory pathways contribute to persistent chronic inflammation in RA. In contrast to nonresponders, etanercept therapy modulated serum cytokine levels and caused a marked decrease of IL-6 levels in responders. IL-21 might be involved in the regulation of autoantibody production in RA.
authors: Center for Molecular Medicine and Stem Cell Research, Medical Faculty, University of Kragujevac, Svetozara Markovica 69, 34000 Kragujevac, Serbia.
authors: Sladjana M
authors: SM
authors: Zivojinovic
authors: Nada N
authors: NN
authors: Pejnovic
authors: Mirjana N
authors: MN
authors: Sefik-Bukilica
authors: Ljiljana V
authors: LV
authors: Kovacevic
authors: Ivan I
authors: II
authors: Soldatovic
authors: Nemanja S
authors: NS
authors: Damjanov
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D016207:Cytokines / Q000097:blood / Q000276:immunology*; D000068800:Etanercept; D005260:Female; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000627:therapeutic use*; D058504:Th17 Cells / Q000166:cytology / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept; D008727:Methotrexate