Background
To evaluate the possible protective effect of sympatholytic medications with respect
to neutrophil function, we evaluated the influence of a nonselective β-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 β2-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 β-blockers abolished the immunomodulatory effects of epinephrine on CD62l and CD11b
expression and the generation of oxidative free radicals.
Conclusion
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 β-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.
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Article info
Publication history
Published online: December 11, 2009
Accepted:
October 6,
2009
Identification
Copyright
© 2010 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
