MIF inhibition as a novel treatment for experimental autoimmune encephalomyelitis

Macrophage Migration Inhibitory Factor (MIF) has previously been shown to be a promising therapeutic target of inhibition for treatment of chronic inflammatory autoimmune diseases such as Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE), a mouse model for MS. MIF is unique in that it is a proinflammatory cytokine upregulated in response to Glucocorticoids (GCs), the predominant treatment for the acute episodes of MS. We investigated the efficacy of recently developed small molecule MIF inhibitors both independently and in conjunction with glucocorticoid treatment in attenuating the clinical disease severity of EAE. EAE was induced in wild type mice followed by treatment with the Dexamethasone (Dex) and a small molecule MIF inhibitor following clinical disease onset. Antigen-specific splenocytes were harvested and cultured for cytokine ELISPOT assay. Small molecule MIF inhibitors were found to be effective at attenuating clinical EAE disease both in conjunction with glucocorticoid treatment and independently of glucocorticoid treatment. Our data demonstrates the effectiveness of small molecule MIF inhibitors at reducing clinical pathology in EAE and we hope this data will serve as a precursor to clinical application of small molecule MIF inhibitors in MS.