beta2-Adrenoceptor blockade partially restores ex vivo TNF production following hemorrhagic shock.
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.
Asehnoune
Karim
K
AP-HP, Univ Paris-Sud, Hôpital Bicêtre, Département d'Anesthésie-Réanimation, EA3540, F-94275 Le Kremlin Bicêtre, France. karim.asehnoune@pbr.aphp.fr
Fitting
Catherine
C
Edouard
Alain R
AR
Minville
Vincent
V
Benhamou
Dan
D
Cavaillon
Jean-Marc
JM
Moine
Pierre
P
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*
D058669:Adrenergic alpha-2 Receptor Antagonists; D016207:Cytokines; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10