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Time-dependent Changes of Markers Associated with Inflammation in the Lungs of Humans Exposed to Ambient Levels of Ozone*^1,2

Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Robert B. Devlin

Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Susanne Becker

Center for Environmental Medicine and Lung Biology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina 27599

Raphael Perez

ABB Environmental Services, Inc., 6320 Quadrangle Drive, Chapel Hill, North Carolina 27514

William F. McDonnell

Health Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina 27711

Acute exposure of humans to 0.4 ppm ozone results in reversible respiratory function 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 biochemical changes indicative of inflammation occur in humans. Changes in neutrophils and PGE₂ have been observed in humans as early as 3 hr (28) and as late as 18 hr post exposure (19). The purpose of this study was to determine whether inflammatory changes occur relatively rapidly (within 1 hr) following exposure to ozone, or if the cascade of events which are initiated by ozone and lead to inflammation, take some time to develop. We exposed 10 healthy volunteers twice: once to filtered air and once to 0.4 ppm ozone. Each exposure lasted for 2 hr at an exercise level of 60 L/min, and bronchoalveolar lavage was performed 1 hr following exposure. The data from this study were compared to those from a previous study in which 10 subjects were exposed to O₃ under identical conditions except that bronchoalveolar lavage was performed 18 hr following exposure. The results of the present study demonstrate that O₃ is capable of inducing rapid cellular and biochemical changes in the lung. These changes were detectable as early as 1 hr following a 2 hr exposure of humans to ozone. The profiles of these changes were different at 1 hr and 18 hr following ozone exposures. Bronchoalveolar lavage fluid had levels of neutrophils, IL-6, and prostaglandin E₂ that were higher at 1 hr than at 18 hr post exposure. On the other hand, the levels of fibronectin and plasminogen activator were found to be higher at 18 hr than at 1 hr after ozone exposure. A temporal association appeared to exist between changes occurring in the biochemical markers and alterations in lung function. Further studies may be useful in determining if a causal relationship exists between these parameters.

Key Words: Bronchoalveolar lavage • cytokines • prostaglandin E2 • permeability • fibronectin • fibrosis • acute exposure

Toxicologic Pathology, Vol. 19, No. 4-1, 406-411 (1991)
DOI: 10.1177/019262339101900409


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