To determine whether granulocyte–macrophage colony‐stimulating factor (GM‐CSF) and macrophage CSF (M‐CSF or CSF‐1) are involved in the methylated bovine serum albumin/interleukin‐1 (mBSA/IL‐1)–induced arthritis model.

Following systemic injection, IL‐1 has been shown to augment a weak inflammatory response to mBSA in murine joints and to induce an acute erosive arthritis. GM‐CSF and M‐CSF have been implicated in inflammatory reactions, including those in joints, and have recently been shown to exacerbate murine arthritis. Since in vitro studies have found that IL‐1 can enhance GM‐CSF and M‐CSF production, we reasoned that they might be playing a part in IL‐1–mediated arthritis. GM‐CSF–deficient (GM‐CSF−/−) and M‐CSF–deficient (op/op) mice were injected intraarticularly with mBSA and subcutaneously with IL‐1. Arthritis was monitored histologically on day 7. Normal mice were also treated intraperitoneally with blocking monoclonal antibodies to GM‐CSF and M‐CSF, and to the M‐CSF receptor. Numbers of macrophages (Mac‐2 and F4/80 staining) were monitored, as was the number of cycling (bromodeoxyuridine‐positive) cells.

GM‐CSF−/− mice and normal mice treated with anti–GM‐CSF antibody did not show IL‐1–induced arthritis progression. There was a dramatic reduction in synovial cellularity, including reduced numbers of macrophages and cycling cells. The op/op mice did not develop mBSA/IL‐1–induced disease, but blocking antibody to M‐CSF or to the M‐CSF receptor failed to diminish disease in normal mice.

GM‐CSF is involved in the IL‐1–induced arthritis that follows mBSA injection; M‐CSF involvement in the model is also suggested, since op/op mice did not develop arthritis. These studies provide the first in vivo evidence for a role of GM‐CSF, and possibly M‐CSF, in the proinflammatory actions of IL‐1.