Tumor necrosis factor blockade differentially affects innate inflammatory and Th17 cytokines in rheumatoid arthritis

J Rheumatol. 2012 Jan;39(1):18-21. doi: 10.3899/jrheum.110697. Epub 2011 Dec 1.

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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / drug therapy*
  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / physiopathology
  • Cytokines / blood
  • Cytokines / immunology*
  • Etanercept
  • Female
  • Humans
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Immunoglobulin G / immunology
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use*
  • Immunosuppressive Agents / immunology
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Inflammation / drug therapy
  • Inflammation / immunology
  • Male
  • Methotrexate / therapeutic use
  • Middle Aged
  • Receptors, Tumor Necrosis Factor / immunology
  • Receptors, Tumor Necrosis Factor / therapeutic use*
  • Th17 Cells / cytology
  • Th17 Cells / immunology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • Tumor Necrosis Factor-alpha / immunology
  • Young Adult

Substances

  • Antirheumatic Agents
  • Cytokines
  • Immunoglobulin G
  • Immunosuppressive Agents
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Etanercept
  • Methotrexate