Induction of an acute erosive monarticular arthritis in mice by interleukin‐1 and methylated bovine serum albumin

Abstract

We examined the effect of interleukin‐1 (IL‐1) administration on a mild and transient inflammatory response in the knees of mice injected intraarticularly with methylated bovine serum albumin (mBSA). Injection of mBSA on day 0 into nonsensitized mice caused a weak inflammatory response confined to the infrapatellar fat pads and involved infiltration by mononuclear cells, neutrophils, and eosinophils. The response developed between days 4 and 7 and resolved by day 28. No erosion of cartilage or subchondral bone was seen. In contrast, mBSA‐treated mice injected with recombinant human IL‐1β subcutaneously in the ipsilateral footpad on days 0–3 developed a severe monarticular arthritis in the antigen‐injected knee. Pannus developed, extending over the articular surfaces, and extensive erosion of cartilage and subchondral bone occurred. Multinucleated giant cells, together with fibrin‐like material, were observed at sites of active bone erosion and debris, and large numbers of neutrophils were seen in the joint space. These pathologic features represent a new arthritis model in which IL‐1 profoundly augments a weak inflammatory response and induces acute erosive joint destruction, supporting the hypothesis that IL‐1 is an important cytokine in the pathogenesis of arthritis.