Independent roles of Macrophage Migration Inhibitory Factor and endogenous, but not exogenous glucocorticoids in regulating leukocyte trafficking

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Abstract
Objectives: Macrophage migration inhibitory factor (MIF) promotes leukocyte recruitment and antagonizes the anti‐inflammatory effects of glucocorticoids (GC). The aim of this study was to examine whether interaction between MIF and GC underlies the ability of MIF to promote leukocyte– endothelial cell (EC) interactions. Methods: Intravital microscopy was used to assess leukocyte‐EC interactions in wild‐type and MIF−/− mice following treatment with lipopolysaccharide (LPS), the GC dexamethasone, and inhibition of endogenous GC, using the GC‐receptor antagonist, RU486. Results: Dexamethasone reduced LPS‐induced leukocyte interactions in wild‐type mice to levels similar to those observed in MIF −/− mice not treated with dexamethasone, whereas in MIF −/− mice, leukocyte interactions were not further inhibited by dexamethasone. RU486 increased LPS‐induced leukocyte adhesion and emigration to a similar extent in both wild‐type and MIF −/− mice, indicating that endogenous GC exert a similar inhibitory effect on leukocyte trafficking in wild‐type and MIF −/− mice. Both MIF deficiency and RU486 treatment reduced VCAM‐1 expression, while neither treatment modulated expression of ICAM‐1 or chemokines CCL2, KC, and MIP‐2. Conclusions: These results suggest that endogenous MIF and GC regulate leukocyte‐EC interactions in vivo reciprocally but through predominantly independent mechanisms, and that the anti‐inflammatory effect of MIF deficiency is comparable to that of exogenous GC.

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