Attenuation of lung inflammation by adrenergic agonists in murine acute lung injury

Anesthesiology. 2001 Oct;95(4):947-53. doi: 10.1097/00000542-200110000-00025.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adrenergic beta-Agonists / administration & dosage
  • Adrenergic beta-Agonists / therapeutic use*
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Chemokine CXCL2
  • Dobutamine / administration & dosage
  • Dobutamine / therapeutic use
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Injections, Intravenous
  • Interleukin-6 / biosynthesis
  • Lung Injury*
  • Mice
  • Monokines / biosynthesis
  • Neutrophil Infiltration / physiology
  • Organ Size
  • Pneumonia / etiology
  • Pneumonia / pathology
  • Pneumonia / prevention & control*
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Adrenergic beta-Agonists
  • Chemokine CXCL2
  • Interleukin-6
  • Monokines
  • RNA, Messenger
  • Dobutamine