Macrophage migration inhibitory factor promotes resistance to glucocorticoids in experimental autoimmune encephalomyelitis (50.12)

Abstract

Abstract Glucocorticoid (GC) treatment is the standard of care for acute attacks of Multiple sclerosis (MS). However, while initially highly efficacious in inducing remission of MS, GCs eventually loose efficacy and overall do not prevent progression of the disease. GCs have the unique property of inducing the release of Macrophage migration inhibitory factor (MIF), a pro-inflammatory cytokine with broad effects on the immune response. Thus, we hypothesized that MIF could play an important role in promoting disease by its unique ability to counter-regulate the immunosuppressive effects of GCs. Testing this question, we found that treatment of MIF knockout mice (KO) with GCs was substantially more efficacious as compared with GC-treatment of Wt mice and resulted in a substantial delay in disease onset and severity of EAE. Histological and immunofluorescence studies showed that inflammatory infiltrates were dramatically reduced in MIF KO mice. Furthermore, thymus and spleen cells from MIF KO mice showed higher extend of apoptosis upon incubation with GCs as compared with Wt mice. The results suggest that the blockade of MIF in combination with GC administration could be a promising strategy for the treatment of MS. Supported by grants NS052177 (NIH) and RG3499 (NMSS).