β2-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 β-adrenergic tone was evaluated. BALB/c mice were hemorrhaged and resuscitated 60 min after hemorrhage. Animals were sacrified 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 β 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 trigerring agent. Finally, this study demonstrates that β 2 -adrenoceptor ligands play an important role in blood leukocyte deactivation to LPS after hemorrhagic shock.