Influence of beta-adrenoceptor antagonists on hemorrhage-induced cellular immune suppression.
Hemorrhagic shock is associated with increasing catecholamine plasma concentrations. Plasma catecholamines are known to affect cellular immune functions. We therefore, investigated the effect of endogenously released catecholamines on lymphocyte distribution (CD4+ lymphocytes, CD8+ lymphocytes, and natural killer (NK) cells), splenocyte apoptosis (Annexin V binding), tumor necrosis factor-alpha (TNF-alpha), and interleukin 10 (IL-10) release during a volume-controlled hemorrhagic shock in mice. Mice received either saline (HEM), the non-selective beta-adrenoceptor antagonist propranolol (PROP; 2 mg/kg i.p.), or the beta1-adrenoceptor antagonist metoprolol (MET; 2 mg/kg i.p.) before induction of hemorrhage. Mice were sacrificed to obtain the spleen and whole blood 1 h after hemorrhage, 1 h after fluid resuscitation, and 24 h after hemorrhage. Flow cytometric analysis revealed an increase in circulating NK cells in the HEM group. This effect was completely abolished by pretreatment with propranolol or metoprolol. Furthermore, administration of either beta-adrenoceptor antagonist led to a decrease of circulating CD8+ lymphocyte numbers. Monitoring of splenocyte apoptosis by determination of Annexin V binding revealed an increase in splenocyte apoptosis 24 h after hemorrhage in the HEM group but not in the animals pretreated with propranolol or metoprolol. Induction of hemorrhage did not affect TNF-alpha or IL-10 plasma concentrations in either experimental group. We conclude that plasma catecholamines affect cellular immunity in the early phase of trauma via a beta-adrenergic pathway.
Oberbeck
Reiner
R
Department of Trauma Surgery, University Hospital of Essen, Germany.
van Griensven
Martijn
M
Nickel
Eike
E
Tschernig
Thomas
T
Wittwer
Tobias
T
Pape
Hans-Christoph
HC
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects; D004195:Disease Models, Animal; D007111:Immunity, Cellular / Q000187:drug effects; D016753:Interleukin-10 / Q000097:blood; D007694:Killer Cells, Natural / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D051379:Mice; D008815:Mice, Inbred Strains; D011433:Propranolol / Q000494:pharmacology; D012771:Shock, Hemorrhagic / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000187:drug effects / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D011433:Propranolol; D008790:Metoprolol