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Endogenous β-Adrenergic Receptors Inhibit Lipopolysaccharide-Induced Pulmonary Cytokine Release and Coagulation

¹ Center for Infection and Immunity Amsterdam (CINIMA), ² Center for Experimental and Molecular Medicine, ³ Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; and ⁴ Department of Biochemical Pharmacology, University of Konstanz, Germany

Correspondence and requests for reprints should be addressed to Tom van der Poll, M.D., Academic Medical Center, Meibergdreef 9, Room G2-130, 1105 AZ Amsterdam, The Netherlands. E-mail: t.vanderpoll{at}amc.uva.nl

β2-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 β-adrenergic receptors in the regulation of lung inflammation induced by instillation via the airways of lipopolysaccharide (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 β-adrenergic antagonist propranolol or saline 30 minutes before and 3 hours after intranasal LPS or LTA administration. LPS and LTA induced a profound inflammatory response in the lungs as reflected by an influx of neutrophils and the release of proinflammatory cytokines and chemokines into bronchoalveolar lavage fluid (BALF). Propranolol inhalation resulted in enhanced LPS-induced lung inflammation, which was reflected by a stronger secretion of TNF-, IL-6, and monocyte chemoattractant protein-1 into BALF and by enhanced coagulation activation (thrombin–antithrombin complexes). In LTA-induced lung inflammation, propranolol did not influence cytokine release but potentiated activation of coagulation. Propranolol did not alter neutrophil recruitment in either model. This study suggests that β-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.

Key Words: lipopolysaccharide • lipoteichoic acid • lung inflammation • β-receptor antagonist • murine model • coagulation

CLINICAL RELEVANCE β-adrenergic receptors are widely expressed in the lung. We provide evidence that these receptors inhibit inflammation and coagulation in the bronchoalveolar space, thereby identifying a novel anti-inflammatory mechanism in the lung.