ObjectiveTo determine whether acid instillation augments tumor necrosis factor-&agr; and nitric oxide production by alveolar macrophages in rats, and to study the effects of treatment with pentoxifylline before acid instillation on the production of these inflammatory mediators.DesignControlled laboratory investigation on tumor necrosis factor-&agr; and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury.SettingUniversity research laboratory.SubjectAlveolar macrophages of rats.InterventionsAlveolar macrophages were recovered by bronchoalveolar lavage at 4, 10, 16, 24, and 72 hrs after unilateral hydrochloric acid (pH, 1.0; volume, 0.1 mL) instillation into the lungs of rats. Alveolar macrophages then were cultured with or without lipopolysaccharide. One group of rats was pretreated with pentoxifylline before acid instillation.Measurements and Main ResultsAlveolar macrophages from both acid-instilled and contralateral lungs, which had recovered 24 hrs after acid instillation, produced significantly greater tumor necrosis factor-&agr; and nitric oxide. Subsequent exposure to lipopolysaccharide, as a surrogate for bacterial infection, further promoted tumor necrosis factor-&agr; and nitric oxide release. Alveolar macrophages from rats pretreated with pentoxifylline before acid instillation produced significantly less tumor necrosis factor-&agr; and did not overproduce tumor necrosis factor-&agr; when exposed to lipopolysaccharide. In contrast, pretreatment with pentoxifylline had no effect on nitric oxide production by alveolar macrophages.ConclusionsAcid instillation stimulates alveolar macrophages to produce tumor necrosis factor-&agr; and nitric oxide. Pentoxifylline preserved innate production of tumor necrosis factor-&agr; to lipopolysaccharide and did not inhibit the production of bactericidal nitric oxide. This may partly explain why pentoxifylline reduces acid aspiration-induced lung injury while maintaining the host’s ability to combat bacterial infection after acid aspiration.