INDUCTION OF CYCLOOXYGENASE-2 IN ALVEOLAR MACROPHAGES AFTER ACID ASPIRATION - SELECTIVE CYCLOOXYGENASE-2 BLOCKADE REDUCES INTERLEUKIN-6 PRODUCTION

Background: Gastric acid aspiration can result in acute lung injury. I n this study, the authors determined whether alveolar macrophages expr ess cyclooxygenase-2 as a source of inflammatory mediators after acid aspiration. Methods: Seventy-five microliters of hydrochloric acid sol ution, pH 1.15, was instilled into one lung in mice. After exposure, a lveolar macrophages were harvested, and competitive polymerase chain r eaction and enzyme-linked immunosorbent assay were performed to measur e expression of cyclooxygenase-1 and -2, interleukin-1 beta and -6, tu mor necrosis factor-alpha, and inducible nitric oxide synthase (iNOS). The authors used immunocytochemistry to demonstrate expression of cyc looxygenase-2 in alveolar macrophages. Selective cyclooxygenase-2 bloc kade using N-2(-cyclohexyloxy-4-nitrophenyl) methane-sulphonamide was done to characterize prostaglandin-cytokine interaction. Results: Acid aspiration induced upregulation of cyclooxygenase-2 and interleukin-6 . Tumor necrosis factor-alpha and iNOS were not upregulated. Interleuk in-1 beta was upregulated even with saline instillation but could not be detected Ln the supernatant of the cell culture. Alveolar macrophag es harvested from mice instilled with acid showed a trend toward more production of prostaglandin E-2 and produced higher concentrations of interleukin-6 compared with alveolar macrophages from mice instilled w ith saline. Selective cyclooxygenase-2 blockade significantly decrease d release of interleukin-6 from alveolar macrophages harvested from mi ce instilled with acid. Conclusions: Acid aspiration induces strong ex pression of cyclooxygenase-2 and production of interleukin-6 in alveol ar macrophages. Selective cyclooxygenase-2 blockade reduced production of interleukin-6 by acid-stimulated alveolar macrophages. These studi es suggest that the induction of cyclooxygenase-2 plays an important r ole in the systemic inflammatory response induced by acid aspiration.