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

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.

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.

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.