Activation of alveolar macrophages in acid-injured lung in rats: Differenteffects of pentoxifylline on tumor necrosis factor-alpha and nitric oxide production

Objective: To determine whether acid instillation augments tumor necrosis f actor-alpha and nitric oxide production by alveolar macrophages in rats, an d to study the effects of treatment with pentoxifylline before acid instill ation on the production of these inflammatory mediators. Design: Controlled laboratory investigation on tumor necrosis factor-a and nitric oxide production by alveolar macrophages of rats that had acid-induc ed lung injury. Setting. University research laboratory. Subject. Alveolar macrophages of rats. Interventions. Alveolar macrophages were recovered by bronchoalveolar lavag e 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 wa s pretreated with pentoxifylline before acid instillation. Measurements and Main Results, Alveolar macrophages from both acid-instille d and contralateral lungs, which had recovered 24 hrs after acid instillati on, produced significantly greater tumor necrosis factor-a and nitric oxide . Subsequent exposure to lipo-polysaccharide, as a surrogate for bacteria[ infection, further promoted tumor necrosis factor-alpha and nitric oxide re lease. Alveolar macrophages from rats pretreated with pentoxifylline before acid instillation produced significantly less tumor necrosis factor-alpha and did not overproduce tumor necrosis factor-a when exposed to lipopolysac charide. In contrast, pretreatment with pentoxifylline had no effect on nit ric oxide production by alveolar macrophages. Conclusions: Acid instillation stimulates alveolar macrophages to produce t umor necrosis factor-alpha and nitric oxide. Pentoxifylline preserved innat e production of tumor necrosis factor-a to lipopolysaccharide and did not i nhibit the production of bactericidal nitric oxide. This may partly explain why pentoxifylline reduces acid aspiration-induced lung injury while maint aining the host's ability to combat bacterial infection after acid aspirati on.