Circulating soluble tumor necrosis factor receptors, interleukin-2 receptors, tumor necrosis factor alpha, and interleukin-6 levels in rheumatoid arthritis. Longitudinal evaluation during methotrexate and azathioprine therapy

Arthritis Rheum. 1993 Aug;36(8):1070-9. doi: 10.1002/art.1780360807.


Objective: To assess whether circulating concentrations of soluble tumor necrosis factor receptors (sTNFR; p55 and p75), soluble interleukin-2 receptors (sIL-2R), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) reflect clinical response and whether changes are dependent on the drug used in rheumatoid arthritis (RA) patients taking methotrexate (MTX) or azathioprine (AZA).

Methods: These cytokines and soluble receptors were assessed in 20 control subjects and serially for up to 48 weeks in 61 RA patients, by bioassay (IL-6) and immunoassays (sTNFR, sIL-2R, TNF alpha, and IL-6).

Results: Concentrations of p55 and p75, sIL-2R, and TNF alpha (but not IL-6) were significantly higher in RA patients than in controls. Significant decreases in sIL-2R and p55 concentrations were associated with clinical improvement and were observed in patients treated with MTX, but not AZA. Both treatments induced decreases in IL-6 concentrations, but circulating AZA (or its metabolites) appears to interfere with the measurement of IL-6 bioactivity. TNF alpha and p75 levels did not show significant changes.

Conclusion: Measurement of circulating sIL-2R, p55, and IL-6 may be useful in the evaluation of RA disease activity and response to therapy. Interference by circulating levels of drugs must be ruled out when bioassays are used to evaluate cytokine levels.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / blood*
  • Arthritis, Rheumatoid / drug therapy
  • Azathioprine / therapeutic use*
  • Cytokines / blood*
  • Double-Blind Method
  • Humans
  • Interleukin-6 / blood
  • Longitudinal Studies
  • Methotrexate / therapeutic use*
  • Prospective Studies
  • Receptors, Cell Surface / analysis
  • Receptors, Interleukin-2 / analysis
  • Receptors, Tumor Necrosis Factor
  • Treatment Outcome
  • Tumor Necrosis Factor-alpha / analysis


  • Cytokines
  • Interleukin-6
  • Receptors, Cell Surface
  • Receptors, Interleukin-2
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • Azathioprine
  • Methotrexate