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

Kelly L. Davenpeck, John Zagorski, Robert P. Schleimer, Bruce S. Bochner*

*Corresponding author for this work

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

A common side effect of high dose glucocorticoid therapy is increased susceptibility to bacterial infection, an effect that is in part mediated through 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 interactions, in response to bacterial LPS, were examined utilizing a model of rat mesenteric intravital microscopy. Pretreatment of rats with DEX (0.5 mg/kg) for 18 h or 30 min before stimulation with LPS significantly inhibited LPS-induced 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-induced neutrophil chemoattractant-1 (CINC-1) generation, since antagonists to these mediators were able to mimic DEX effects on leukocyte- endothelial interactions and circulating leukocyte phenotype. These data indicate that inhibition of cytokine- and chemokine-induced leukocyte- endothelial interactions may be a primary mechanism by which glucocorticoids inhibit leukocyte recruitment to bacterial agents and thus increase susceptibility to infection.

Original languageEnglish (US)
Pages (from-to)6861-6870
Number of pages10
JournalJournal of Immunology
Volume161
Issue number12
StatePublished - Dec 15 1998

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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