Am. J. Respir. Crit. Care Med.,
Volume 162, Number 4, October 2000, 1366-1371
Acid Instillation Enhances the Inflammatory
Response to Subsequent Lipopolysaccharide
Challenge in Rats
HIROSHI
YAMADA,
HIROSHI
MIYAZAKI,
TATSUAKI
KIKUCHI,
JUNICHI
FUJIMOTO,
and
ICHIDAI
KUDOH
Department of Anesthesiology, Yokohama City University School of Medicine, Yokohama, Japan
Aspiration of gastric contents is one of leading causes of the acute
respiratory distress syndrome (ARDS). The pathogenesis of acid
aspiration-induced acute lung injury is well understood. Less clear
is why patients who have suffered acid aspiration are susceptible
to ARDS. We studied the effects of acid instillation on the inflammatory response to subsequent lipopolysaccharide (LPS) challenge in rats. Instillation of acid into the right lung worsened the
pathology induced by LPS that was administered 24 h after acid
instillation. This included worsened oxygenation, increased pulmonary edema, increased production of tumor necrosis factor-alpha (TNF-
) and cytokine-induced neutrophil chemoattractant, neutrophil accumulation and mobilization to the alveolar spaces, and nitric oxide (NO) production. Of interest, neutrophil mobilization, NO production, and protein permeability were also magnified in the left lung. These effects were attenuated by administration of the protein tyrosine kinase (PTK) inhibitors genistein and tyrphostin AG556. These data suggest that acid instillation primes the rat to enhance the inflammatory response to subsequent endotoxin challenge and that at least part of the augmented inflammatory response depends on PTK.