Macrophage migration inhibitory factor (MIF): A multifaceted cytokine regulated by genetic and physiological strategies

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine encoded within a functionally polymorphic genetic locus. MIF was initially recognized as a cytokine generated by activated T cells, but in recent days it has been identified as a multipotent key cytokine secreted by many other cell types involved in immune response and physiological processes. MIF is a highly conserved 12.5 kDa secretory protein that is involved in numerous biological processes. The expression and secretion profile of MIF suggests that MIF to be ubiquitously and constitutively expressed in almost all mammalian cells and is vital for numerous physiological processes. MIF is a critical upstream mediator of host innate and adaptive immunity and survival pathways resulting in the clearance of pathogens thus playing a protective role during infectious diseases. On the other hand, MIF being an immune modulator accelerates detrimental inflammation, promotes cancer metastasis and progression, thus worsening disease conditions. Several reports demonstrated that genetic and physiological factors, including MIF gene polymorphisms, posttranslational regulations, and receptor binding control the functional activities of MIF. Taking into consideration the multi-faceted role of MIF both in physiology and pathology, we thought it is timely to review and summarize the expressional and functional regulation of MIF, its functional mechanisms associated with its beneficial and pathological roles, and MIF-targeting therapies. Thus, our review will provide an overview on how MIF is regulated, its response, and the potency of the therapies that target MIF.