Therapeutic opportunities for antagonism of macrophage migration inhibitory factor.

Abstract

Macrophage migration inhibitory factor (MIF) is a pleiotropic pro-inflammatory cytokine, expressed in many tissues and upregulated in a number of inflammatory diseases and models of inflammation. In common with many cytokines, it is a product of the hypothalamo-pituitary-adrenal (HPA) axis as well as of inflammatory cells in the activated immune system. MIF, however, is uniquely identified as a glucocorticoid-induced pro-inflammatory cytokine, which acts to counterbalance glucocorticoid anti-inflammatory effects. The broad range of effects of MIF in inflammatory disease, combined with its glucocorticoid-antagonist properties, suggest it as a therapeutic target in inflammatory diseases, especially those in which glucocorticoids are currently used. This paper reviews the biology of MIF and evidence for its potential as a therapeutic target, as well as the currently available literature regarding potential MIF-antagonist therapeutic modalities.