Cycloxygenase inhibition enhances the effects of surfactant therapy in endotoxin-induced rat model of ARDS.

Abstract

The present study examines the relationships between inflammation and surfactant protein (SP) expression in a rodent model of acute respiratory distress syndrome (ARDS). Rats were intratracheally instilled with lipopolysaccharide (LPS) for 72 hours to induce ARDS and further treated with exogenous surfactant. Prostaglandin E(2) (PGE(2)) levels, cycloxygenase (COX) activity and alterations in SP-A apoprotein were measured. COX and SP-A expressions in lung tissue and SP-A-positive cells were determined by Western blot and immunofluorescence, respectively. PGE(2) levels and COX activity and its expression were increased with LPS exposure, whereas SP-A protein and percentage of SP-A-positive cells were decreased, which were subsequently reverted back by exogenous surfactant instillation. Because inhibition of COX-2 action is proposed to be useful in various inflammatory lung injuries, these results suggest that COX-2 expression and the possible beneficial effects of its inhibition on lung inflammation and dysfunction with LPS-ARDS corresponds closely with reduced SP-A expression.