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(American Journal of Pathology. 2003;162:47-56.)
© 2003 American Society for Investigative Pathology

Regular Articles

Regulation of Macrophage Migration Inhibitory Factor Expression by Glucocorticoids in Vivo

Gunter Fingerle-Rowson^*, Peter Koch, Rachel Bikoff^*, Xinchun Lin^*, Christine N. Metz^*, Firdaus S. Dhabhar, Andreas Meinhardt and Richard Bucala^*¶

From The Picower Institute for Medical Research,^*Manhasset, New York; the Colleges of Medicine and Dentistry,Ohio State University, Columbus, Ohio; the Yale University School of Medicine,^¶New Haven, Connecticut; the Gene Center of Ludwig-Maximilians University,Munich, Germany; and the Department of Anatomy and Cell Biology,Justus-Liebig-University, Giessen, Germany

Glucocorticoid hormones are important anti-inflammatory agents because of their anti-inflammatory and proapoptotic action within the immune system. Their clinical usefulness remains limited however by side effects that result in part from their growth inhibitory action on sensitive target tissues. The protein mediator, macrophage migration inhibitory factor (MIF), is an important regulator of the host immune response and exhibits both glucocorticoid-antagonistic and growth-regulatory properties. MIF has been shown to contribute significantly to the development of immunopathology in several models of inflammatory disease. Although there is emerging evidence for a functional interaction between MIF and glucocorticoids in vitro, little is known about their reciprocal influence in vivo. We investigated the expression of MIF in rat tissues after ablation of the hypothalamic-pituitary-adrenal axis and after high-dose glucocorticoid administration. MIF expression is constitutive and independent of the influence of adrenal hormones. Hypophysectomy and the attendent loss of pituitary hormones, by contrast, decreased MIF protein content in the adrenal gland. Administration of dexamethasone was found to increase MIF protein expression in those organs that are considered to be sensitive to the growth inhibitory effects of glucocorticoids (immune and endocrine tissues, skin, and muscle). This increase was most likely because of a posttranscriptional regulatory effect because tissue MIF mRNA levels were not influenced by dexamethasone treatment. Finally, MIF immunoneutralization enhanced lymphocyte egress from blood during stress-induced lymphocyte redistribution, consistent with a functional interaction between MIF and glucocorticoids on immune cell trafficking in vivo. These findings suggest a role for MIF in both the homeostatic and physiological action of glucocorticoids in vivo.

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