Macrophage migration inhibitory factor: a counter-regulator of glucocorticoid action and critical mediator of septic shock.
Recent studies have led to the discovery of a mediator that acts as an endogenous counter-regulator of glucocorticoid action within the immune system. Isolated as a product of anterior pituitary cells, this protein was found to have the sequence of macrophage migration inhibitory factor (MIF), one of the first cytokine activities to be described. Macrophages and T cells release MIF in response both to various inflammatory stimuli and upon incubation with low concentrations of glucocorticoids. The glucocorticoid-induced secretion of MIF is tightly regulated and decreases at high, anti-inflammatory steroid concentrations. Once secreted, MIF "overrides" the anti-inflammatory and immunosuppressive effects of steroids on macrophage and T-cell cytokine production. The physiological role of MIF thus appears to be to counter-balance steroid inhibition of the inflammatory response. Anti-MIF antibodies fully protect animals from experimentally induced gram-negative or gram-positive septic shock, an effect that may be the result of the increased anti-inflammatory effects of glucocorticoids after neutralization of endogenous MIF. Anti-MIF therapeutic strategies are presently under development and may prove to be a means to modulate cytokine production in septic shock as well as in other inflammatory disease states.
Calandra
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T
Picower Institute for Medical Research, Manhasset, New York 11030, USA.
Bucala
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R
D000276:Adjuvants, Immunologic; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005938:Glucocorticoids / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011965:Receptors, Glucocorticoid / Q000276:immunology / Q000378:metabolism*; D012772:Shock, Septic / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D005938:Glucocorticoids; D008263:Macrophage Migration-Inhibitory Factors; D011965:Receptors, Glucocorticoid