ENHANCED PRODUCTION OF INTERLEUKIN-1, TUMOR-NECROSIS-FACTOR-ALPHA, AND FIBRONECTIN BY RAT LUNG PHAGOCYTES FOLLOWING INHALATION OF A PULMONARY IRRITANT

Interleukin-1 (IL-1), tumor necrosis factor-alpha (TNF-alpha), and fib ronectin are macrophage-derived mediators thought to be important in t he pathogenesis of lung injury, inflammation, and fibrosis. In the pre sent studies, we examined the effects of acute exposure of rats to the pulmonary irritant, ozone (O-3), on production of these mediators by lung phagocytes. Cells were isolated from lungs 48 h after exposure of rats to air or O-3 (2 ppm, 3 h). We found that cells from O-3-exposed rats released 2- to 3-fold more IL-1 and TNF-alpha into the culture m edium than did cells from air-exposed rats. These effects were time de pendent, reaching a maximum at 2 and 24 h for IL-1, and 2 to 4 h for T NF-alpha. We also found that alveolar macrophages from O-3-treated rat s produced increased amounts of fibronectin, both alone and in respons e to transforming growth factor-beta, lipopolysaccharide, and interfer on-gamma when compared with cells from control rats. Examination of im munohistochemically stained tissue sections indicated increased IL-1, TNF-alpha, and fibronectin in lungs from O-3-exposed animals when comp ared with control animals. IL-1 and TNF-alpha were localized in lung m acrophages, whereas fibronectin was associated with blood vessel walls and the lung interstitium. These results demonstrate that lung phagoc yte production of these inflammatory mediators is elevated following O -3 exposure and suggest that they may play a role in oxidant-induced p ulmonary inflammation and injury.