title: Anti-TNF therapy reduces serum levels of chemerin in rheumatoid arthritis: a new mechanism by which anti-TNF might reduce inflammation.
abstract: BACKGROUND
  Chemerin is a specific chemoattractant for macrophages and dendritic cells (DC). In addition, it can rapidly stimulate macrophage adhesion to extracellular matrix proteins and adhesion molecules and is able to activate fibroblast-like synoviocytes (FLS), suggesting a role in the pathogenesis of rheumatoid arthritis (RA). Chemerin is also an adipocytokine that has been related to the inflammatory state of endothelial cells and as such could be involved in the changes in endothelial cells in RA and perhaps increased cardiovascular morbidity. We investigated whether anti-Tumor Necrosis Factor (TNF) treatment affects chemerin levels.
  
  
  METHODS
  49 patients with active RA (disease activity score evaluated in 28 joints (DAS28) ≥3.2) were started on adalimumab therapy. Blood was drawn from patients while fasting at baseline and 16 weeks after initiation of treatment. Chemerin serum levels were measured by ELISA and related to disease activity, mediators of inflammation and known risk factors for cardiovascular disease.
  
  
  RESULTS
  Adalimumab therapy reduced chemerin serum levels, which was correlated with the reduction in DAS28 (r = 0.37, p = 0.009). In addition, the decrease in chemerin serum levels after anti-TNF treatment was associated with the decrease in serum levels of IL-6 (r = 0.39, p = 0.033) and macrophage migration inhibitory factor (MIF) (r = 0.31, p = 0.049). Baseline chemerin serum levels were not related to traditional risk factors for atherosclerosis, except perhaps for smoking (p = 0.07).
  
  
  CONCLUSIONS
  This exploratory study shows that adalimumab therapy lowers chemerin levels, which is associated with the reduction in disease activity parameters, and inflammatory mediators IL-6 and MIF. This suggests a possible involvement of chemerin in the migration/retention of macrophages in the synovium. TRIAL REGISTRATION NEDERLANDS TRIAL REGISTER: NTR 857.
authors: Department of Clinical Immunology and Rheumatology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.m.herenius@amc.uva.nl
authors: Marieke M J
authors: MM
authors: Herenius
authors: Ana S F
authors: AS
authors: Oliveira
authors: Carla A
authors: CA
authors: Wijbrandts
authors: Daniëlle M
authors: DM
authors: Gerlag
authors: Paul P
authors: PP
authors: Tak
authors: Maria C
authors: MC
authors: Lebre
mesh_terms: D000068879:Adalimumab; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy*; D050197:Atherosclerosis / Q000097:blood / Q000473:pathology; D018925:Chemokines / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000188:drug therapy*; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6 / Q000097:blood; D008263:Macrophage Migration-Inhibitory Factors / Q000097:blood; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D018925:Chemokines; D036341:Intercellular Signaling Peptides and Proteins; D015850:Interleukin-6; D008263:Macrophage Migration-Inhibitory Factors; C478630:RARRES2 protein, human; D014409:Tumor Necrosis Factor-alpha; D000068879:Adalimumab