Endothelin antagonists new bullets against lung injury.docVIP

Available online /content/9/3/245 Commentary Endothelin antagonists: new bullets against lung injury? Marc Leeman Laboratory of Physiology, Faculty of Medicine, Erasme Campus of the Free University of Brussels, Belgium Corresponding author: Marc Leeman, marc.leeman@ulb.ac.be Published online: 14 April 2005 Critical Care 2005, 9:245-246 (DOI 10.1186/cc3525) This article is online at /content/9/3/245 ? 2005 BioMed Central Ltd See related research by Kuklin et al. in this issue [/content/9/3/R211] Abstract The American–European consensus conference on ARDS defined ALI/ARDS as a “syndrome of inflammation and increased permeability”. Hence, it is now widely accepted that the pathophysiology of ALI/ARDS is driven by an aggressive inflammatory reaction that damages the alveolo- capillary unit [2,3,5,6]. The inflammatory response includes both cellular and humoral components. After rapid recruit- ment of leukocytes to the inflamed site, there is activation of mediator cascades including the production of cytokines, chemokines, acute phase proteins, free radicals, complement, coagulation pathway components and focal upregulation of adhesion molecule expression units [5,6]. Several cytokines, such as tumor necrosis factor alpha (TNF-α), interleukin (IL)-1, IL-6 and IL-8, have been found in bronchoalveolar lavage fluid and plasma of patients with ARDS [3,5]. Inflammatory mediators amplify endothelial injury directly or by recruiting inflammatory cells into the vascular, interstitial and alveolar spaces [3,5]. Acute lung injury is a syndrome of inflammation and of increased permeability of the blood–gas barrier. Endothelins are thought to exert proinflammatory effects. Kuklin and colleagues show that the endothelin receptor antagonist tezosentan reduces pulmonary edema in endotoxemic sheep, in parallel with a prevention of prote