Activation of alveolar macrophages in acid-injured lung in rats: different effects of pentoxifylline on tumor necrosis factor-alpha and nitric oxide production.
OBJECTIVE
To determine whether acid instillation augments tumor necrosis factor-alpha 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.


METHODS
Controlled laboratory investigation on tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury.


METHODS
University research laboratory.


METHODS
Alveolar macrophages of rats.


METHODS
Alveolar 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.


RESULTS
Alveolar macrophages from both acid-instilled and contralateral lungs, which had recovered 24 hrs after acid instillation, produced significantly greater tumor necrosis factor-alpha and nitric oxide. Subsequent exposure to lipopolysaccharide, as a surrogate for bacterial infection, further promoted tumor necrosis factor-alpha and nitric oxide release. Alveolar macrophages from rats pretreated with pentoxifylline before acid instillation produced significantly less tumor necrosis factor-alpha and did not overproduce tumor necrosis factor-alpha when exposed to lipopolysaccharide. In contrast, pretreatment with pentoxifylline had no effect on nitric oxide production by alveolar macrophages.


CONCLUSIONS
Acid instillation stimulates alveolar macrophages to produce tumor necrosis factor-alpha and nitric oxide. Pentoxifylline preserved innate production of tumor necrosis factor-alpha 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.
Kudoh
I
I
Department of Anesthesiology, Yokohama City University School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. ikudoh@med.yokohama-cu.ac.jp
Miyazaki
H
H
Ohara
M
M
Fukushima
J
J
Tazawa
T
T
Yamada
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D006851:Hydrochloric Acid / Q000633:toxicity*; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D010431:Pentoxifylline / Q000494:pharmacology*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D010726:Phosphodiesterase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D006851:Hydrochloric Acid; D010431:Pentoxifylline