Constitutively expressed by a broad spectrum of cells and tissues, including monocytes and macrophages, the cytokine macrophage migration inhibitory factor (MIF) is rapidly released after exposure to microbial products and pro-inflammatory mediators, and in response to stress. After it is released, MIF induces pro-inflammatory biological responses that act as a regulator of immune responses. MIF activates the extracellular signal-regulated kinase 1 (ERK1)/ERK2–mitogen-activated protein kinase pathway, inhibits the activity of JUN activation domain-binding protein 1 (JAB1) - a co-activator of the activator protein 1 (AP1) - upregulates the expression of Toll-like receptor 4 to promote the recognition of endotoxin-expressing bacterial pathogens, sustains pro-inflammatory function by inhibiting p53-dependent apoptosis of macrophages and counter-regulates the immunosuppressive effects of glucocorticoids on immune cells[1].

[1] T Calandra et al. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat Rev Immunol. 2003 Oct;3(10):791-800.