Macrophage migration inhibitory factor is released from pituitary folliculo-stellate-like cells by endotoxin and dexamethasone and attenuates the steroid-induced inhibition of interleukin 6 release
T Tierney1, R Patel1, CS Stead1, L Leng2, R Bucala2 & JC Buckingham1
Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine produced by peripheral immune cells and also by pituitary endocrine cells. MIF exerts its pro-inflammatory actions in the host defence system by blocking the inhibitory effects of glucocorticoids on the release of other pro-inflammatory cytokines. Reports that pituitary folliculo-stellate (FS) cells show characteristics of immune cells led us to propose that FS cells may serve as an additional source of MIF in the pituitary and that pituitary-derived MIF may act locally to modulate endotoxin-induced cytokine release from FS cells. Here we address this hypothesis by using (a) immunohistochemistry to localise MIF in primary pituitary tissue and (b) well characterised FS (TtT/GF), corticotroph (AtT20) and macrophage/monocyte (RAW 264.7) cell lines to explore the effects of CRH, endotoxin and dexamethasone on MIF release and to examine the effects of MIF on IL-6 release. Our immunohistochemical study showed that MIF is abundant in S100-positive FS cells and is also present in other pituitary cell types. All three cell lines expressed MIF protein and responded over 24h to endotoxin and dexamethasone with concentration-dependent increases in MIF release. CRH also stimulated MIF release from AtT20 cells but, unlike endotoxin and dexamethasone, did not effect MIF release from TtT/GF or RAW cells. Recombinant MIF had no effect on basal IL-6 release from TtT/GF cells but reversed the inhibitory effects of dexamethasone on endotoxin-induced IL-6 from these cells. The results suggest that FS cells are both a source of and a target for MIF and raise the possibility that MIF serves as a paracrine/autocrine factor in the pituitary gland that contributes to the protective neuroendocrine response to endotoxin.
Generously supported by the Wellcome Trust.