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

Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in inflammatory and immune responses. MIF was originally discovered as a lymphokine involved in delayed hypersensitivity and various 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 ubiquitously expressed in various organs, such as the brain and kidney. Among cytokines, 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 physiologic significance remains to be elucidated. It was demonstrated that anti-MIF antibodies effectively suppress tumor growth and tumor-associated angiogenesis, suggesting that MIF is involved not only in inflammatory and immune responses but also in tumor cell growth. At present, MIF cannot be clearly categorized as either a cytokine, hormone, or enzyme. This review presents 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 potential functions in various pathophysiologic states.