Affiliation:
1. *Clinical Assistant Professor, ‡Fellow in Critical Care Medicine, §Professor, University of British Columbia Program of Critical Care Medicine and McDonald Research Laboratories, St. Paul’s Hospital.†Clinical Assistant Professor, Department of Anesthesiology and Intensive Care, University of Kuopio.
Abstract
Background
Acute lung injury leading to a systemic inflammatory response greatly increases mortality in critically ill patients. Cardiovascular management of these patients frequently involves beta-adrenergic agonists. These agents may alter the inflammatory response. Therefore, the authors tested the hypothesis that beta-adrenergic agonists alter the pulmonary inflammatory response during acute lung injury in mice.
Methods
Five-week-old CD-1 mice received continuous infusions of 10 microg x kg(-1) x min(-1) dobutamine, 6 microg x kg(-1) x min(-1) dopexamine, or vehicle via intraperitoneal mini osmotic pumps, followed immediately by intratracheal instillation of approximately 2 microg/kg endotoxin (or phosphate-buffered saline control). Six hours later the mice were killed, and lung lavage was performed. Interleukin-6 and -10 concentrations in lung homogenates were measured using enzyme-linked immunosorbent assay. Interleukin-6 and macrophage inflammatory protein-2 mRNA was measured using reverse-transcription polymerase chain reaction.
Results
Interleukin-6 protein and mRNA significantly increased after intratracheal endotoxin (P < 0.001), and the fraction of neutrophils in lung lavage fluid increased in endotoxin-treated (41 +/- 25%) versus control mice (2 +/- 4%, P < 0.05). Treatment of endotoxic mice with dobutamine significantly decreased interleukin-6 protein (P < 0.05) and mRNA (P < 0.05) expression. Dopexamine had similar but less pronounced effects. Dobutamine decreased interleukin-10 expression, whereas dopexamine did not. In endotoxemic mice, both dobutamine and dopexamine decreased induction of macrophage inflammatory protein-2 mRNA (P < 0.05) and reduced the fraction of neutrophils in lung lavage fluid (P < 0.05).
Conclusions
In endotoxin-induced acute lung injury, beta-adrenergic agonists can significantly decrease proinflammatory cytokine expression, decrease induction of chemokine mRNA, and decrease the resultant neutrophil infiltrate in the lung.
Publisher
Ovid Technologies (Wolters Kluwer Health)
Subject
Anesthesiology and Pain Medicine
Cited by
34 articles.
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