Macrophage migration inhibitory factor promotes central nervous system pathology in a model of neuroinflammation (35.8)

Abstract

Abstract Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system (CNS). Cerebrospinal fluid collected from MS patients during relapse was found to contain greater levels of macrophage migration inhibitory factor (MIF) than samples collected during remission. We have shown that induction of experimental autoimmune encephalomyelitis (EAE) in MIF-deficient mice results in reduced clinical signs and CNS inflammatory infiltrates relative to wild type controls. However, there was no difference in T cell function in the periphery between the two groups. These findings suggest that MIF acts within the CNS to potentiate disease progression. The potent pro-inflammatory properties of MIF are well established; however, the precise contribution of MIF to neuroinflammation is not well defined. MIF is expressed by many cell types in the CNS including infiltrating macrophages and resident microglia, suggesting that MIF may enhance the inflammatory environment of MS lesions. To assess the contribution of MIF to CNS inflammation, primary microglial cultures were treated with increasing doses of rMIF, which upregulated inflammatory mediators associated with MS and EAE: IL-1β, iNOS, and CCL2. We are currently exploring the role of MIF in vivo using an intraspinal model of neuroinflammation. Taken together, these data suggest that inhibition of MIF may serve as a therapeutic strategy for resolving CNS inflammation.