Activation of alveolar macrophages in acid-injured lung in rats: Different effects of pentoxifylline on tumor necrosis factor-α and nitric oxide production
- 1 August 2001
- journal article
- Published by Ovid Technologies (Wolters Kluwer Health) in Critical Care Medicine
- Vol. 29 (8), 1621-1625
- https://doi.org/10.1097/00003246-200108000-00020
Abstract
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. Controlled laboratory investigation on tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury. University research laboratory. Alveolar macrophages of rats. 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. 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. 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.Keywords
This publication has 27 references indexed in Scilit:
- Systemic inflammatory response syndromeBritish Journal of Surgery, 1997
- Pentoxifylline attenuates LPS-induced bronchial hyperresponsiveness but not the increase in exhaled nitric oxideClinical and Experimental Allergy, 1997
- Acid aspiration-induced lung injury in rabbits is mediated by interleukin-8-dependent mechanisms.JCI Insight, 1995
- The Effect of Pentoxifylline on Acid-induced Alveolar Epithelial InjuryAnesthesiology, 1995
- Ethanol suppresses LPS-induced mRNA for nitric oxide synthase II in alveolar macrophages in vivo and in vitroAlcohol, 1994
- Tumor Necrosis Factor-Alpha: Central Regulatory Cytokine in the Induction of Macrophage Antimicrobial ActivitiesPathobiology, 1991
- Tumor Necrosis Factor-α Mediates Acid Aspiration-induced Systemic Organ InjuryAnnals of Surgery, 1990
- Adverse Respiratory Events in Anesthesia: A Closed Claims AnalysisAnesthesiology, 1990
- Aspiration during anaesthesia: a computer‐aided study of 185 358 anaestheticsActa Anaesthesiologica Scandinavica, 1986
- Clinical predictors of the adult respiratory distress syndromeThe American Journal of Surgery, 1982