MIF

Description

Although first described as a soluble activity produced by activated T cells nearly four decades ago, interest in macrophage migration inhibitory factor (MIF) was rekindled when the mouse homolog of this protein was identified to be secreted from the anterior pituitary gland in a hormone-like fashion (Bernhagen et aL, 1993). Initially. MIF was shown to play a critical role in the host inflammatory response to endotoxin. Further studies showed that the inflammatory activity of MIF was mediated by its ability to promote proinflammatory cytokine release (Calandra et aL. 1994) and to suppress the anti-inflammatory effects of glucocorticoids (Calandra et aL. 1995; Bacher et aL. 1996). Since the identification of MIF as a unique proinflammatory molecule and the development of neutralizing monoclonal antibodies, several reports have been published describing the role of MIF in inflammatory diseases, including arthritis, glomerulonephritis, peritonitis, and the delayed-type hypersensitivity reaction. Clinical evidence demonstrating increased MIF expression during inflammatory disease pathogenesis further supports the potential role of MIF in inflammation. In addition to its role in the inflammatory response. MIF has been shown to exhibit growth-promoting activities. Recent investigations by two independent laboratories have revealed that immunoneulralization of MIF can inhibit tumor growth and angiogenesis (Chesney et a!.. 1999; Shimizu et aL, 1999b). Further-more, MIF has been shown to inactivate p53. a potent tumor suppressor molecule (Hudson et aL. 1999) supporting the role of MIF in cellular proliferation. Several chronic inflammatory conditions are associated with the development of tumors. Therefore, the identification of MIF as a suppressor of p53 activity might provide a mechanistic link between inflammation and tumorigenesis.