H. Yamada et al., Acid instillation enhances the inflammatory response to subsequent lipopolysaccharide challenge in rats, AM J R CRIT, 162(4), 2000, pp. 1366-1371
Aspiration of gastric contents is one of leading causes of the acute respir
atory 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 lipopolysacch
aride (LPS) challenge in rats. Instillation of acid into the right lung wor
sened the pathology induced by LPS that was administered 24 h after acid in
stillation. This included worsened oxygenation, increased pulmonary edema,
increased production of tumor necrosis factor-alpha (TNF-alpha) and cytokin
e-induced neutrophil chemoattractant, neutrophil accumulation and mobilizat
ion 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 A
G556. These data suggest that acid instillation primes the rat to enhance t
he inflammatory response to subsequent endotoxin challenge and that at leas
t part of the augmented inflammatory response depends on PTK.