macrophage migration inhibitory factor; MIF; glycosylation-inhibiting factor; GIF; L-dopachrome isomerase; L-dopachrome tautomerase; phenylpyruvate tautomerase (MIF, GLIF, MMIF)

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Function

pro-inflammatory cytokine
involved in the innate immune response to bacterial pathogens
expression of MMIF at sites of inflammation suggests a role as mediator in regulating macrophages in host defense
counteracts the anti-inflammatory activity of glucocorticoids
has phenylpyruvate tautomerase & dopachrome tautomerase activity (in vitro)
- physiological substrate is unknown
- not clear whether the tautomerase activity has any physiological relevance, or whether it is important for cytokine activity
interacts with CXCR2 extracellular domain
interacts with the CD74 extracellular domain, COPS5 & BNIPL

secreted, cytoplasm
does not have a cleavable signal sequence & is secreted via a specialized, non-classical pathway
secreted by macrophages upon stimulation by bacterial lipopolysaccharide (LPS), or by M tuberculosis antigens

genetic variations in MMIF are associated with susceptibility to juvenile rheumatoid arthritis
serum levels of MMIF are elevated in patients with severe sepsis or septic shock
- high levels of plasma MMIF are correlated with low survival
- drugs that inhibit tautomerase activity protect against death due to sepsis