title: beta2-Adrenoceptor blockade partially restores ex vivo TNF production following hemorrhagic shock.
abstract: The aim of the study was to assess the mechanisms through which leukocyte deactivation occurs upon hemorrhagic shock. In particular, the influence of beta-adrenergic tone was evaluated. BALB/c mice were hemorrhaged and resuscitated 60 min after hemorrhage. Animals were sacrificed 60 min later by exsanguination. Blood from exsanguination was cultured ex vivo with lipopolysaccharide (LPS) and heat-killed Staphylococcus aureus Cowan I (SAC). Hemorrhage resulted in a major decrease of LPS-induced TNF production whereas IL-10 production was significantly enhanced. Selective beta(2)-adrenoceptor antagonists (ICI 118,551) attenuated the decrease in TNF production and further enhanced IL-10 production. Hemorrhage did not alter SAC-induced TNF production levels whereas IL-10 production was increased. ICI 118,551 further increased the production of both TNF and IL-10. These data suggest that leukocyte deactivation after LPS stimulation is not a generalized phenomenon since TNF production was maintained when another microbial activator was used. IL-10 production was enhanced after hemorrhagic shock, independently of the nature of the triggering agent. Finally, this study demonstrates that beta(2)-adrenoceptor ligands play an important role in blood leukocyte deactivation to LPS after hemorrhagic shock.
authors.affiliation: AP-HP, Univ Paris-Sud, Hôpital Bicêtre, Département d'Anesthésie-Réanimation, EA3540, F-94275 Le Kremlin Bicêtre, France. karim.asehnoune@pbr.aphp.fr
authors.forename: Karim
authors.initials: K
authors.lastname: Asehnoune
authors.forename: Catherine
authors.initials: C
authors.lastname: Fitting
authors.forename: Alain R
authors.initials: AR
authors.lastname: Edouard
authors.forename: Vincent
authors.initials: V
authors.lastname: Minville
authors.forename: Dan
authors.initials: D
authors.lastname: Benhamou
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Cavaillon
authors.forename: Pierre
authors.initials: P
authors.lastname: Moine
mesh_terms: D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012771:Shock, Hemorrhagic / Q000097:blood* / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000097:blood*
chemical_list: D058669:Adrenergic alpha-2 Receptor Antagonists; D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10