This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (6) Citing Articles via Google Scholar Google Scholar Articles by Loop, T. Articles by Pannen, B. H. J. Search for Related Content PubMed PubMed Citation Articles by Loop, T. Articles by Pannen, B. H. J. Related Collections Critical Care Pharmacology

---

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.

This article has been cited by other articles:

				J. L. Vega, H. Keino, and S. Masli Surgical Denervation of Ocular Sympathetic Afferents Decreases Local Transforming Growth Factor-{beta} and Abolishes Immune Privilege Am. J. Pathol., September 1, 2009; 175(3): 1218 - 1225. [Abstract] [Full Text] [PDF]

				N. W. Kin and V. M. Sanders It takes nerve to tell T and B cells what to do J. Leukoc. Biol., June 1, 2006; 79(6): 1093 - 1104. [Abstract] [Full Text] [PDF]