Role of macrophage migration inhibitory factor (MIF) in murine antigen‐induced arthritis: interaction with glucocorticoids

(MIF) is a broad‐spectrum proinflammatory cytokine implicated in human rheumatoid arthritis. The synthesis of MIF by synovial cells is stimulated by glucocorticoids, and previous studies suggest that MIF antagonizes the anti‐inflammatory effects of glucocorticoids. This has not been established in a model of arthritis. We wished to test the hypothesis that MIF can act to reverse the anti‐inflammatory effects of glucocorticoids in murine antigen‐induced arthritis (AIA). Cutaneous DTH reactions and AIA were induced by intradermal injection and intra‐articular injection, respectively, of methylated bovine serum albumin in presensitized mice. Animals were treated with anti‐MIF MoAbs, recombinant MIF, and/or dexamethasone (DEX). Skin thickness of DTH reactions was measured with callipers and arthritis severity was measured by blinded quantitative histological assessment of synovial cellularity. Cutaneous DTH to the disease‐initiating antigen was significantly inhibited by anti‐MIF MoAb treatment (P