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Pharmacologic Therapies on the Horizon for Acute Lung Injury/Acute Respiratory Distress Syndrome
  1. Jeffrey R. Jacobson, MD
  1. From the Section of Pulmonary and Critical Care Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL.
  1. Received July 30, 2009, and in revised form September 3, 2009.
  2. Accepted for publication September 3, 2009.
  3. Reprints: Jeffrey R. Jacobson, MD, Section of Pulmonary and Critical Care Medicine, Pritzker School of Medicine, University of Chicago, Chicago, IL. E-mail: jjacobso{at}medicine.bsd.uchicago.edu.
  4. This work acknowledges support from the Parker B. Francis Foundation, and the symposium was supported in part by a grant from the National Center for Research Resources (R13 RR023236).

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a spectrum of diseases that are commonly encountered in the intensive care unit and are associated with high mortality. Although significant advances have been made with respect to the ventilatory management of patients with ALI/ARDS with proven beneficial effects on outcomes, pharmacologic therapies remain nonexistent. Because the cardinal feature of ALI/ARDS is an increase in lung vascular permeability, often precipitated by an exuberant inflammatory response with subsequent endothelial barrier disruption, strategies aimed at promoting endothelial barrier function could serve as novel therapies in this setting. We have identified several promising agonists in this regard including sphingosine 1-phosphate, activated protein C, and statins, a class of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. These agonists all have in common the ability to directly mediate endothelial cell signaling and induce characteristic actin cytoskeletal rearrangement leading to endothelial cell barrier protection. Our in vitro findings have been extended to animal models of ALI/ARDS and suggest that effective pharmacologic therapies for patients with ALI/ARDS may soon be available.

Key Words
  • sphingosine 1-phosphate
  • activated protein C
  • statins
  • permeability
  • ALI/ARDS
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