MIF as a glucocorticoid-induced modulator of cytokine production

Abstract

GLUCOCORTICOID hormones are important for vital functions and act to modulate inflammatory and immune responses1, 2. Yet, in contrast to other hormonal systems, no endogenous mediators have been identified that can directly counter-regulate their potent anti-inflammatory and immunosuppressive properties. Recent investigations of the protein macrophage migration inhibitory factor (MIF), which was discovered originally to be a T-lymphocyte-derived factor3, 4, have established it to be a pro-inflammatory pituitary and macrophage cytokine and a critical mediator of septic shock5–7. Here we report the unexpected finding that low con-centrations of glucocorticoids induce rather than inhibit MIF production from macrophages. MIF then acts to override gluco-corticoid-mediated inhibition of cytokine secretion by lipopoly-saccharide (LPS)-stimulated monocytes and to overcome glucocorticoid protection against lethal endotoxaemia. These observations identify a unique counter-regulatory system that functions to control inflammatory and immune responses. © 1995, Nature Publishing Groups. All Rights Reserved.