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Renal/Inflammation/Protection

ACE inhibitors enalaprilat and quinaprilat inhibit monocyte surface receptor expression: 100

Welters, I. D.; Reyher, C.; Hafer, G.; Hempelmann, G.; Menzebach, A.; Müller, M.; Heidt, M. C.

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European Journal of Anaesthesiology: June 2004 - Volume 21 - Issue - p 7

Introduction: Cardiac surgery with or without cardiopulmonary bypass (CPB) leads to activation of cellular as well as humoral components of the immune response. The majority of patients with coronary artery disease are treated with ACE inhibitors to optimize afterload. However, the possible immunomodulating effects of ACE inhibitors remain to be elucidated. The aim of this study was to investigate anti-inflammatory effects of the ACE inhibitors enalaprilat and quinaprilat on spontaneous and LPS-induced monocyte surface receptor expression.

Method: The study was approved by the local ethical board. After informed consent 100 μL whole blood from 12 healthy donors was incubated with different concentrations of enalaprilat and quinaprilat for 15 and 180 minutes respectively, where indicated, aliquots were stimulated with 100 ng/mL LPS. Blood incubated with a FITC-labelled non-specific antibody against IgG served as a control and for flow cytometer setup. Fluoresceine isothiocyanate (FITC) labelled antibodies against LPS receptor CD 14 and complement receptor 3 (CD11b/CD18) were used for determination of surface receptor expression. Median fluorescence intensities were determined to assess receptor expression.

Results: Enalaprilat and quinaprilat inhibited spontaneous CD14 expression in a time and concentration dependent manner:

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This decrease in CD14 expression correlated well with a reduced spontaneous CD11b expression:

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LPS-induced CD11b expression was also significantly inhibited:

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Discussion: Immunoinhibitory effects of ACE inhibitors are at least partly mediated by reduced surface receptor expression. This anti-inflammatory mechanism may attenuate cell damage in ischaemia/reperfusion [1] syndromes as well as CPB-induced immune responses or cytokine production [2]. Further clinical studies are warranted to investigate whether CPB-induced monocyte activation may be influenced by pre- or intraoperative administration of ACE inhibitors.

References:

1 Guba M, Steinbauer M, Buchner M, et al. Differential effects of short-term ace- and AT1-receptor inhibition on postischemic injury and leukocyte adherence in vivo and in vitro. Shock 2000; 13: 190-196.
2 Schindler R, Dinarello CA, Koch KM. Angiotensin-converting-enzyme inhibitors suppress synthesis of tumour necrosis factor and interleukin 1 by human peripheral blood mononuclear cells. Cytokine 1995; 7: 526-533.
© 2004 European Society of Anaesthesiology