Dependence of interleukin-1-induced arthritis on granulocyte-macrophage colony-stimulating factor

Objective, To determine whether granulocyte-macrophage colony-stimulating f actor (GM-CSF) and macrophage CSF (M-CSF or CSF-1) are involved in the meth ylated bovine serum albumin/interleukin-1 (mBSA/IL-1)-induced arthritis mod el. Methods. Following systemic injection, IL-1 has been shown to augment a wea k inflammatory response to mBSA in murine joints and to induce an acute ero sive arthritis. GM-CSF and M-CSF have been implicated in inflammatory react ions, 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-deficien t (op/op) mice were injected intraarticularly with mBSA and subcutaneously with IL-1, Arthritis was monitored histologically on day 7, Normal mice wer e 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 (bromodeoxyur idine-positive) cells. Results, GM-CSF-/- mice and normal mice treated with anti-GM-CSF antibody d id not show IL-1-induced arthritis progression. There was a dramatic reduct ion in synovial cellularity, including reduced numbers of macrophages and c ycling 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 dis ease in normal mice. Conclusion. GM-CSF is involved in the IL-1-induced arthritis that follows m BSA injection; M-CSF involvement in the model is also suggested, since op/o p mice did not develop arthritis. These studies provide the first in vivo e vidence for a role of GM-CSF, and possibly M-CSF, in the proinflammatory ac tions of IL-1.