Macrophage Migration Inhibitory Factor is Involved in the Pathogenesis of Collagen Type II-induced Arthritis in Mice

To determine the importance of macrophage migration inhibitory factor (MIF) in the development of arthritis we used an experimental model for rheumatoid arthritis, collagen type II (CII)-induced arthritis in mice. Treatment with neutralizing anti-MIF Abs before immunization of (B10.Q x DBA/1)F1 with CII led to delayed onset and lowered frequency of arthritis. This was associated with lower levels of IgG2a to CII in MIF-depleted mice. The proliferative response to CII was stronger in the anti-MIF-treated mice, whereas no significant effects were seen on Ag-induced IFN-gamma production in response to CII or on the total serum Ab levels in response to CII. These results provide the first experimental evidence of a role for MIF in the pathogenesis of autoimmune disease.