title: Analysis of SF and plasma cytokines provides insights into the mechanisms of inflammatory arthritis and may predict response to therapy.
abstract: OBJECTIVE
  Biologic drugs have revolutionized the care of RA, but are expensive and not universally effective. To further understand the inflammatory mechanisms underlying RA and identify potential biomarkers predicting response to therapy, we measured multiple cytokine concentrations in SF of patients with inflammatory arthritides (IAs) and, in a subset of patients with RA, correlated this with response to TNF-α inhibition.
  
  
  METHODS
  SF from 42 RA patients and 19 non-RA IA patients were analysed for 12 cytokines using a multiplex cytokine assay. Cytokines were also measured in the plasma of 16 RA patients before and following treatment with anti-TNF-α. Data were analysed using Mann-Whitney U-test, Spearman's rank correlation and cluster analysis with the Kruskal-Wallis test with Dunn's post-test analysis.
  
  
  RESULTS
  RA SF contained significantly elevated levels of IL-1β, IL-1ra, IL-2, IL-4, IL-8, IL-10, IL-17, IFN-γ, G-CSF, GM-CSF and TNF-α compared with other IA SF. RA patients who did not respond to anti-TNF therapy had elevated IL-6 in their SF pre-therapy (P < 0.05), whereas responders had elevated IL-2 and G-CSF (P < 0.05). Plasma cytokine concentrations were not significantly modulated by TNF inhibitors, with the exception of IL-6, which decreased after 12 weeks (P < 0.05).
  
  
  CONCLUSIONS
  Cytokine profiles in RA SF vary with treatment and response to therapy. Cytokine concentrations are significantly lower in plasma than in SF and relatively unchanged by TNF inhibitor therapy. Concentrations of IL-6, IL-2 and G-CSF in SF may predict response to TNF inhibitors.
authors.affiliation: University of Liverpool, Liverpool, UK.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Wright
authors.forename: Roger C
authors.initials: RC
authors.lastname: Bucknall
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Moots
authors.forename: Steven W
authors.initials: SW
authors.lastname: Edwards
mesh_terms: D000328:Adult; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000097:blood* / Q000188:drug therapy / Q000378:metabolism; D016022:Case-Control Studies; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood*; D004359:Drug Therapy, Combination; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000378:metabolism; D006801:Humans; D007376:Interleukin-2 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D013582:Synovial Fluid / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000627:therapeutic use
chemical_list: D018501:Antirheumatic Agents; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor