Diazepam decreases leukocyte-endothelium interactions in situ

Author(s)

Lazzarini, R. ; Sakai, M. ; Costa-Pinto, F. A. ; Palermo-Neto, J. ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Med Vet & Zootecnia, Dept Pathol, Neuroimmunomodulat Res Grp, Lab Farmacol Aplicada & Toxicol, Sch Vet Med & Ani, BR-05508000 Sao Paulo - Brazil

• Document type: Journal article
• Source: Immunopharmacology and Immunotoxicology; v. 32, n. 3, p. 402-409, SEP 2010.
• Web of Science Citations: 9

Abstract

High doses of diazepam reduce the inflammatory paw edema in rats. This effect was attributed to an action of diazepam on the Translocator Protein (TSPO). We evaluated the effects of diazepam (10 mg/kg, intraperitoneally) on leukocyte rolling and migration. In carrageenan-induced acute inflammation, diazepam decreased the interaction of leukocytes with endothelial cells (rolling) and the number of leukocytes in the mesentery (migration). RU486 (antagonist of glucocorticoid receptors) reduced the effects of diazepam on leukocyte rolling and migration, suggesting a participation of endogenous corticosteroids. We also showed that the effects of diazepam on leukocyte-endothelium interactions are mediated by nitric oxide (NO), since prior treatment with l-arginine (precursor of NO) partially precludes the inhibitory effects of diazepam; conversely, pretreatment with L-NAME (false substrate of the NO synthase) somewhat potentiates the effects of diazepam. The pathways that underlie the effects of diazepam remain to be further elucidated, but we believe that both local and systemic mechanisms may overlap to explain the influence of diazepam on leukocyte-endothelium interactions. (AU)

• FAPESP's process: 04/14128-0 - Neuroimmunomodulation: effects of drugs, stress and cytocines on central nervous and immune systems bidirectional relationships
• Grantee: João Palermo Neto
• Support Opportunities: Research Projects - Thematic Grants