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CRITICAL CARE AND TRAUMA

Dobutamine Inhibits Phorbol-Myristate-Acetate-Induced Activation of Nuclear Factor-B in Human T Lymphocytes In Vitro

Department of Anesthesiology and Critical Care Medicine, University Hospital, Freiburg, Germany

Address correspondence and reprint requests to Benedikt H. J. Pannen, MD, Anaesthesiologische Universitätsklinik Hugstetterstrasse 55, D-79106 Freiburg, Germany. Address e-mail to pannen{at}nz11.ukl.uni-freiburg.de

Adrenergic drugs are often used for hemodynamic support of cardiac output and vasomotor tone in critically ill patients. Recent evidence shows that the administration of these vasoactive drugs may affect cytokine release and could influence the inflammatory response. However, the mechanism of this immunomodulatory effect remains unknown. The nuclear transcription factor-B (NF-B) regulates the expression of many cytokines and plays a central role in the immune response. Therefore, we examined the effects of various adrenergic drugs (dobutamine, xamoterol, clenbuterol, epinephrine, norepinephrine, and phenylephrine) on the activation of NF-B, on the NF-B-driven reporter gene activity, and on the expression of the NF-B target gene interleukin (IL)-8. In addition, we quantified the amount of the NF-B inhibitors IB and IL-10. Here we report that dobutamine inhibited the activation of NF-B in primary human CD3⁺ T lymphocytes. Suppression of NF-B involved the stabilization of its inhibitor, IB. The effect appears to be ß₂-receptor specific, because ß₁-adrenergic and -adrenergic substances (i.e., xamoterol, epinephrine, norepinephrine, and phenylephrine) did not affect NF-B activation and because dobutamine-mediated inhibition of NF-B could be prevented by a specific ß₂-antagonist. Our results demonstrate that dobutamine is a potent and specific inhibitor of NF-B, and they thus provide a possible molecular mechanism for the immunomodulation associated with ß-adrenergic therapy.

IMPLICATIONS: Dobutamine is a specific inhibitor of nuclear factor-B, which may provide a molecular mechanism for the immunomodulation associated with ß-adrenergic therapy.

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Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999