Submitted on December 4, 2007
Revised on April 10, 2008
Endogenous 
Adrenergic Receptors Inhibit LPS-induced Pulmonary Cytokine Release and Coagulation
Ida A.J. Giebelen1, Masja Leendertse1, Mark C Dessing1, Joost C.M. Meijers2, Marcel Levi2, Christian Draing3, Sonja von Aulock3, and Tom van der Poll1*
1 Academic Medical Center, University of Amsterdam, Center for Infection and Immunity Amsterdam (CINIMA), Amsterdam, The Netherlands; Academic Medical Center, University of Amsterdam, Center for Experimental and Molecular Medicine, Amsterdam, The Netherlands,
2 Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands,
3 Department of Biochemical Pharmacology, University of Konstanz, Konstanz, Germany
* To whom correspondence should be addressed. E-mail: t.vanderpoll{at}AMC.UVA.NL.
2 adrenergic receptors are expressed on different cell types in the lung including respiratory epithelial cells, smooth muscle cells and macrophages. The aim of the current study was to determine the role of adrenergic receptors in the regulation of lung inflammation induced by instillation via the airways of either LPS (a constituent of the Gram-negative bacterial cell wall) or lipoteichoic acid (LTA, a component of the Gram-positive bacterial cell wall). Mice inhaled the adrenergic antagonist propranolol or saline 30 minutes before and 3 h after intranasal LPS or LTA administration. LPS and LTA both induced a profound inflammatory response in the lungs as reflected by influx of neutrophils and release of proinflammatory cytokines and chemokines into bronchoalveolar lavage fluid (BALF). Propranolol inhalation resulted in enhanced LPS-induced lung inflammation which was reflected in particular by a stronger secretion of tumor necrosis factor-
, interleukin-6 and monocyte chemoattractant protein-1 into BALF, and enhanced coagulation activation (thrombin-antithrombin complexes). In LTA-induced lung inflammation propranolol did not influence cytokine release but also potentiated activation of coagulation. Propranolol did not alter neutrophil recruitment in either model. This study suggests that adrenergic receptors, which are widely expressed in the lungs, serve as negative regulators of pulmonary cytokine release and coagulation induced by LPS and less so during LTA-induced pulmonary inflammation.
