Macrophage migration inhibitory factor (MIF): Its essential role in the immune system and cell growth

Macrophage migration inhibitory factor (MIF) functions as a pleiotropic pro tein, participating in inflammatory and immune responses. MIF was originall y discovered as a lymphokine involved in delayed hypersensitivity and vario us macrophage functions, including phagocytosis, spreading, and tumoricidal activity, Recently, MIF was reevaluated as a proinflammatory cytokine and pituitary-derived hormone potentiating endotoxemia. This protein is ubiquit ously expressed in various organs, such as the brain and kidney. Among cyto kines, MIF is unique in terms of its abundant expression and storage within the cytoplasm and, further, for its counteraction against glucocorticoids. MIF has unexpectedly been found to convert D-dopachrome, an enantiomer of naturally occurring L-dopachrome, to 5,6-dihydroxyindole, However, its phys iologic significance remains to be elucidated. It was demonstrated that ant i-MIF antibodies effectively suppress tumor growth and tumor-associated ang iogenesis, suggesting that MIF is involved not only in inflammatory and imm une responses but also in tumor cell growth. At present, MIF cannot be clea rly categorized as either a cytokine, hormone, or enzyme. This review prese nts the latest findings on the role of MIF in the immune system and in cell growth, with regard to tumorigenesis and wound repair, and discusses its p otential functions in various pathophysiologic states.