Dexamethasone inhibits leukocyte emigration in rat mesenteric post-capillary venules: an intravital microscopy study.
The effect of subcutaneous administration of dexamethasone (DEX) on interleukin-1beta(IL-1beta, 20 ng i.p., - 2 h) and platelet-activating factor (PAF, 100 nM in superfusion) -induced leukocyte interaction with the endothelium of rat mesenteric post-capillary venules was studied. DEX produced a dose-dependent inhibition of IL-1beta-induced leukocyte extravasation in the rat mesenteric vascular bed, with a calculated ED5o of 40 microg/kg and a maximal effect of 80-100% inhibition at 0.1 mg/kg. IL-1beta-induced cell adhesion to post-capillary venules was only partially inhibited by the steroid, with a calculated ED50 of 480 microg/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 microg/kg DEX (which was inactive when given as a single injection) resulted again in a selective inhibition of IL-1beta-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.
Tailor
A
A
Department of Biochemical Pharmacology, The William Harvey Research Institute, London, United Kingdom.
Flower
R J
RJ
Perretti
M
M
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D007375:Interleukin-1 / Q000494:pharmacology; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects*; D008853:Microscopy; D010972:Platelet Activating Factor / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013152:Splanchnic Circulation
D005938:Glucocorticoids; D007375:Interleukin-1; D010972:Platelet Activating Factor; D003907:Dexamethasone