Restoration of neutrophil immunocompetence after cardiopulmonary bypass by beta-adrenergic blockers.
BACKGROUND
To evaluate the possible protective effect of sympatholytic medications with respect to neutrophil function, we evaluated the influence of a nonselective beta-blocker medication on the interaction of neutrophils and epinephrine after cardiopulmonary bypass. Therefore, we studied the importance of adrenoceptors for the immunomodulation of neutrophils by catecholamines in vitro.


METHODS
First, we investigated the modulation of neutrophils from healthy volunteers, after stimulation with n-formyl-l-methionyl-l-leucyl-l-phenylalanin (FMLP) in the presence of epinephrine with or without the addition of one of the following adrenergic receptor antagonists: atenolol, butoxamine, pindolol, prazosin, or RS79984. The second part included an investigation of the modulation of neutrophils from patients after operative coronary revascularization with or without extracorporeal circulation after stimulation with FMLP and addition of epinephrine. After loading with anti-CD62l or anti-CD11b antibodies or dihydrorhodamine, the expression of CD62l and CD11b and generation of oxidative free radicals were assessed by flow cytometry.


RESULTS
The suppression of oxidative free radical generation, inhibition of CD62l downregulation after stimulation with FMLP, and suppression of CD11b upregulation after FMLP stimulation from epinephrine were all mediated by beta(2)-adrenoceptors. After cardiac surgery with cardiopulmonary bypass, epinephrine inhibited the CD62l downregulation, the suppression of CD11b upregulation, and the generation of oxidative free radicals after FMLP stimulation. The pre-operative administration of beta-blockers abolished the immunomodulatory effects of epinephrine on CD62l and CD11b expression and the generation of oxidative free radicals.


CONCLUSIONS
The immunomodulatory effects of epinephrine on neutrophils remained unchanged irrespective of cardiopulmonary bypass and could contribute to the detrimental effects of epinephrine after heart surgery. The preoperative administration of nonselective beta-blockers abolished the immunomodulatory effects of epinephrine in vitro and in patients, and it enhanced the immunocompetence of neutrophils in a context of increased catecholamine levels.
Trabold
Benedikt
B
Department of Anesthesiology, University Medical Center, Regensburg, Germany. benedikt.trabold@klinik.uni-regensburg.de
Lunz
Dirk
D
Gruber
Michael
M
Froehlich
Dieter
D
Graf
Bernhard
B
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001262:Atenolol / Q000494:pharmacology; D002078:Butoxamine / Q000494:pharmacology; D002395:Catecholamines / Q000097:blood; D001026:Coronary Artery Bypass / Q000706:statistics & numerical data*; D016207:Cytokines / Q000097:blood; D004837:Epinephrine / Q000494:pharmacology; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D007121:Immunocompetence; D007546:Isoquinolines / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009287:Naphthyridines / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D010869:Pindolol / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D016207:Cytokines; D005609:Free Radicals; D007546:Isoquinolines; D009287:Naphthyridines; C104875:RS 79948-197; D002078:Butoxamine; D001262:Atenolol; D009240:N-Formylmethionine Leucyl-Phenylalanine; D010869:Pindolol; D011224:Prazosin; D004837:Epinephrine