Lipopolysaccharide-induced leukocyte rolling and adhesion in the rat mesenteric microcirculation: Regulation by glucocorticoids and role of cytokines

A common side effect of high dose glucocorticoid therapy is increased susce ptibility to bacterial infection, an effect that is in part mediated throug h inhibition of leukocyte recruitment to infected areas, However, the sites at which glucocorticoids act to prevent the multistep process of leukocyte recruitment have not been fully established. In this study, the effects of the glucocorticoid dexamethasone (DEX) on leukocyte-endothelial interactio ns, in response to bacterial LPS, were examined utilizing a model of rat me senteric intravital microscopy, Pretreatment of rats with DEX (0.5 mg/kg) f or 18 h or 30 min before stimulation with LPS significantly inhibited LPS-i nduced leukocyte rolling and adhesion in mesenteric postcapillary venules, Pretreatment with DEX also inhibited LPS-induced changes in expression of L -selectin and a shared epitope of CD11b/c on circulating neutrophils. These effects of DEX may be due to DEX inhibition of IL-1, TNF, and cytokine-ind uced neutrophil chemoattractant-l (CINC-1) generation, since antagonists to these mediators were able to mimic DEX effects on leukocyte-endothelial in teractions and circulating leukocyte phenotype. These data indicate that in hibition of cytokine- and chemokine-induced leukocyte-endothelial interacti ons may be a primary mechanism by which glucocorticoids inhibit leukocyte r ecruitment to bacterial agents and thus increase susceptibility to infectio n.