TIME-DEPENDENT CHANGES OF INFLAMMATORY MEDIATORS IN THE LUNGS OF HUMANS EXPOSED TO 0.4 PPM OZONE FOR 2 HR - A COMPARISON OF MEDIATORS FOUNDIN BRONCHOALVEOLAR LAVAGE FLUID 1 AND 18 HR AFTER EXPOSURE

Acute exposure of humans to ozone results in reversible respiratory fu nction decrements and cellular and biochemical changes leading to the production of substances which can mediate inflammation and acute lung injury. While pulmonary function decrements occur almost immediately after ozone exposure, it is not known how quickly the cellular and bio chemical changes indicative of inflammation occur in humans. Increased bronchoalveolar lavage (BAL) fluid levels of neutrophils (PMNs) and p rostaglandins (PGE(2)) have been reported in humans as early as 3 hr a nd as late as 18 hr after exposure. The purpose of this study was to d etermine whether a broad range of inflammatory mediators are elevated in BAL fluid within 1 hr of exposure. We exposed eight healthy volunte ers twice: once to 0.4 ppm ozone and once to filtered air. Each exposu re lasted for 2 hr during which the subjects underwent intermittent he avy exercise (66 liters/min). BAL was performed 1 hr after the exposur e. Ozone induced rapid increases in PMNs, total protein, LDH, alpha-1 antitrypsin, fibronectin, PGE(2), thromboxane B-2, C3a, tissue factor, and clotting factor VII. In addition, there was a decrease in the rec overy of total cells and alveolar macrophages, and decreased ability o f alveolar macrophages to phagocytize Candida albicans. A comparison o f these changes with changes observed in an earlier study in which sub jects underwent BAL 18 hr after an identical exposure regimen indicate s that IL-6 and PGE(2) levels were higher 1 hr after exposure than 18 hr after exposure, fibronectin and tissue-plasminogen activator levels were higher 18 hr after exposure, and that PMNs, protein, and C3a wer e present at essentially the same levels at both times. These results indicate that (i) several inflammatory mediators are already elevated 1 hr after exposure; (ii) some mediators achieve their maximal levels in BAL fluid at different times following exposure. These data suggest that the inflammatory response is complex, depending on a cascade of timed events, and that depending on the mediator of interest one must choose an appropriate sampling time. (C) 1996 Academic Press, Inc.