Blockage of interleukin-6 receptor ameliorates joint disease in murine collagen-induced arthritis

Arthritis Rheum. 1998 Dec;41(12):2117-21. doi: 10.1002/1529-0131(199812)41:12<2117::AID-ART6>3.0.CO;2-P.


Objective: To clarify the role of interleukin-6 (IL-6) in the pathogenesis of collagen-induced arthritis (CIA).

Methods: CIA was induced by immunizing twice at a 3-week interval with bovine type II collagen (CII) emulsified with complete adjuvant. Rat anti-mouse IL-6 receptor (anti-IL-6R) monoclonal antibody MR16-1 or isotype-matched control antibody KH-5 was then injected once intraperitoneally. Symptoms of arthritis were evaluated with a visual scoring system, and serum anti-CII antibody and IL-6 levels were measured by enzyme-linked immunosorbent assay. In addition, the CII responsiveness of splenic lymphocytes from mice with CIA was examined.

Results: In mice with CIA, excess production of IL-6 in sera was observed within 24 hours after the first CII immunization, and then rapidly decreased. Serum IL-6 increased again beginning 14 days after immunization, in conjunction with the onset of arthritis. When MR16-1 was injected immediately after immunization with CII, it inhibited the development of arthritis in a dose-dependent manner. Furthermore, MR16-1-treated mice exhibited lower serum levels of IgG anti-CII antibody and reduced responsiveness of lymphocytes to CII. This suppressive effect was observed when MR16-1 was injected on day 0 or 3, but not when injected on day 7 or 14.

Conclusion: IL-6 produced after CII immunization appears to play an essential role in the immunity to CII, and anti-IL-6R antibody reduces the development of CIA by suppressing IL-6 signal transduction.

MeSH terms

  • Animals
  • Antibodies / blood
  • Antibodies, Monoclonal / pharmacology
  • Arthritis, Rheumatoid / chemically induced*
  • Collagen / immunology
  • Disease Models, Animal
  • Interleukin-6 / blood
  • Joint Diseases / complications*
  • Lymphocytes / immunology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Receptors, Interleukin-6 / antagonists & inhibitors*
  • Receptors, Interleukin-6 / immunology
  • Spleen / cytology


  • Antibodies
  • Antibodies, Monoclonal
  • Interleukin-6
  • Receptors, Interleukin-6
  • Collagen