Dexamethasone inhibits leukocyte emigration in rat mesenteric post-capillary venules: An intravital microscopy study

The effect of subcutaneous administration of dexamethasone (DEX) on interleukin-1 beta (IL-1 beta, 20 ng i.p., -2 h) and platelet-activating factor (PAF, 100 nMin superfusion) -induced leukocyte interaction with the endothelium of rat mesenteric post-capillary venules was studied. DEX produced a dose-dependent inhibition of IL-1 beta-induced leukocyte extravasation in the rat mesenteric vascular bed, with a calculated ED50 of 40 mu g/kg and a maximal effect of 80-100% inhibition at 0.1 mg/kg. IL-1 beta-induced cell adhesion to post-capillary venules was only partially inhibited by the steroid, with a calculated ED50 of 480 mu g/kg and a maximal effect of 40-60% inhibition. Furthermore, the steroid inhibited leukocyte emigration, but not adhesion, caused by superfusion of the mesenteric vascular bed with PAF. A doubling of leukocyte emigration time (from 226 to 552 s) was observed after treatment of rats with DEX. Administration for 5 days of a dose of 10 mu g/kg DEX (which was inactive when given as a single injection) resulted again in a selective inhibition of IL-1 beta-induced leukocyte emigration, without effect on cell adhesion. These data demonstrate a preferential susceptibility of the leukocyte emigration process to the inhibitory action of DEX.