Synonyms: L-dopachrome isomerase | MMIF

Compound class: Endogenous peptide in human, mouse or rat

Comment: Macrophage migration inhibitory factor (MIF) is an immunoregulatory mediator that has been reported in the literature as a cytokine [2], enzyme [22], hormone [6], chemokine [3], molecular chaperone [7], and molecular redox switch [15,23,27], although the relevance of some of these functions to human biology remains to be fully ascertained. What is undisputed is that MIF is a crucial upstream regulator of a number of cellular processes that when dysregulated can be pathogenic in a variety of inflammatory conditions such as sepsis, rheumatoid arthritis, inflammatory bowel disease, and multiple sclerosis. It exhibits diverse immunological and neuroendocrine activities, and has been implicated in infectious and autoimmune diseases [11,19,25,28], and it contributes to cancer via its inflammatory, chemotactic, and proliferative actions [4,17,21].
Structurally MIF is believed to exist predominantly as a homotrimer [26], although the discovery that a small MIF peptide fragment can mimic some of the biological activity of the full-length protein [20] suggests that a functional role for the monomer cannot be ruled out. MIF's active tautomerase site forms at the interface of monomer subunits in the trimer [16], and this catalytic site was the first to be targeted for inhibitor design.
MIF is reported to act as an endogenous counter-regulator of the anti-inflammatory effects of glucocorticoids. In relation to this action, MIF inhibitors are reported to produce additive effects with glucocorticoids. This synergism has been reported between the low potency MIF inhibitor iguratimod and glucocorticoids in vivo, as an observed attenuation of experimental autoimmune encephalitis, a model of multiple sclerosis [5].

Species: Human