The diverse actions of macrophage migration inhibitory factor (MIF) within the immuno-neuroendocrine system are yet to be fully understood, but it is clear that MIF plays a pivotal role in the regulation of both the innate and adaptive immune response. An emerging body of data presently indicates that MIF's position within the cytokine cascade is to act in concert with glucocorticoids to control the 'set point' and magnitude of the immune and inflammatory response. In this article we will review the actions of MIF within the immune system and discuss the overlapping and contrasting aspects of MIF and glucocorticoid biology. In particular we will focus on the role of MIF within the immuno-neuroendocrine interface and suggest molecular mechanisms by which MIF may counter-regulate glucocorticoid function. Finally we will discuss emerging evidence that functional MIF gene-promoter polymorphisms render one susceptible to elevated MIF expression, and the development of an exaggerated immune/inflammatory response that potentiates the progression to chronic inflammatory disease.
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