INFLAMMATION AND CELL DAMAGE INDUCED BY REPEATED EXPOSURE OF HUMANS TO OZONE

Abstract

Humans exposed to ozone a single time develop decrements in lung function and an inflammatory reaction in the lung characterized by increased numbers of neutrophils and increased amounts of soluble mediators of inflammation such as interleukin (IL)-8, IL-6, prostaglandin (PG) E, lactate dehydrogenase, elastase, and lung protein in bron2 choalveolar lavage fluid (BALF). However, humans who undergo repeated daily expo- sures to ozone have decrements in lung function on days 1 and 2 of exposure, followed by progressive diminution or even complete disappearance on following days, a process termed "attenuation" or "tolerance." It is not known whether repeated exposure of humans to ozone also results in attenuation of the inflammatory response. In this study, 16 healthy young adult males were exposed to air and 0.4 ppm ozone for 2 h/day on 5 consecutive days, and again a single time 10 or 20 days after the initial 5-day ozone exposure. Bronchoalveolar lavage (BAL) was performed after 5 days of ozone exposure, after 5 days of air exposure, and a third time after the 10- or 20-day follow-up ozone exposure. Ozone-induced increases in percent polymorphonuclear leukocytes (PMNs) and BALF levels of IL-6, PGE, elastase, and fibronectin were diminished after 5 days of expo2 sure. In addition, ozone-induced decreases in recovery of viable BALF cells and alveolar macrophage phagocytosis of yeast were also blunted. However, lactate dehydrogenase (LDH), elastase, IL-8, BALF total protein, 1-antitrypsin, and percent epithelial cells were not diminished. Reversal of ozone-induced attenuation was complex. Some mediators (PMNs, IL-6, PGE, fibronectin, recovery of viable cells) showed at least partial, if not complete, reversal within 10-20 days, while others (total protein, 1-antitrypsin) did not return to the normal response to ozone even after 20 days. We conclude from this study that increases in many cellular and biochemical mediators indicative of inflammation seen after a single exposure of humans to ozone are attenuated after 5 consecutive days of exposure. This attenuation is similar to attenuation of symptoms and lung function reported previously. However, markers of cell injury (increased epithelial cells, LDH, total protein) are not attenuated, and may indicate a persistent but not perceived effect of ozone.