HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 287/3/C730    most recent 00562.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Deng, J. Articles by Jones, S. B. Search for Related Content PubMed PubMed Citation Articles by Deng, J. Articles by Jones, S. B.

RECEPTORS AND SIGNAL TRANSDUCTION

Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis

Departments of ¹Physiology and ²Surgery, The Burn and Shock Trauma Institute, Loyola University Medical Center, Maywood, Illinois 60153

Submitted 10 December 2003 ; accepted in final form 4 May 2004

Enhanced adrenergic stimulation and catecholamine release are important components of the pathophysiology of sepsis. Under physiological conditions, adrenergic stimulation has been shown to be a negative regulator of proinflammatory cytokine production through increasing IL-10 production. Here we have investigated if adrenergic stimulation similarly inhibits TNF- and IL-6 production by splenic macrophages isolated from a polymicrobial sepsis model. Male B₆D₂F₁ mice were subjected to sham (S), laparotomy (Lap), and cecal ligation and puncture (CLP) under anesthesia. Splenic macrophages were isolated 72 h after the initial injury and were stimulated with endotoxin (LPS) in the presence and absence of epinephrine. Compared with S and Lap, splenic macrophages from the CLP group produced significantly less TNF- and IL-6 and more IL-10 when stimulated with LPS. Macrophage cultures from CLP animals incubated with either epinephrine or IL-10 for 2 h had significantly reduced TNF- and IL-6 release in response to LPS. However, similar cultures pretreated with IL-10 antibody before the addition of exogenous epinephrine failed to reverse the attenuation of LPS-stimulated cytokines. Pretreatment of macrophage cultures with ₂- (ICI-118551) but not ₁-adrenergic (atenolol) receptor antagonists reversed the epinephrine-mediated cytokine attenuation following LPS treatment. Data are also presented that demonstrate the involvement of protein kinase A activation with adrenergic agonist but not with IL-10 stimulation. Taken together, these findings suggest that adrenergic mechanisms may influence peripheral tissue macrophage inflammatory cytokine response following trauma and sepsis, independent of the effects of IL-10.

catecholamines; sympathetic; cecal ligation and puncture; bacterial endotoxin; -antagonist

This article has been cited by other articles:

				C. von Montfort, J. I. Beier, L. Guo, J. P. Kaiser, and G. E. Arteel Contribution of the sympathetic hormone epinephrine to the sensitizing effect of ethanol on LPS-induced liver damage in mice Am J Physiol Gastrointest Liver Physiol, May 1, 2008; 294(5): G1227 - G1234. [Abstract] [Full Text] [PDF]