Mechanism(s) of Lung Injury Caused by Perfluoroisobutylene and Related Agents

摘要

This project initially focused on investigations concerning the toxicity ofperfluoroisobutylene (PFIB)-induced lung damage, with emphasis on the chemical reactivity of PFIB with biological constituents. Although the precise mechanism(s) by which PFIB mediates its toxic effects in the lung have as yet to be unequivocally delineated, substantial information was obtained about its target sites in the lung and about products of PFIB that are and are not formed in situ. A subsequent, second phase of the project concerned the mechanistic bases for the pulmonary toxicity of phosgene and the development of prophylactic and/or therapeutic strategies for situations in which exposures of military personnel to this toxic gas may occur. This part of the project revealed the sites of lung injury at the ultrastructural level caused by the acute inhalation of phosgene. Tumor necrosis factor-a production by alveolar macrophages was ruled out as a component of the early pulmonary edematous response to phosgene. Finally, numerous pharmacological approaches for limiting the severity of the pulmonary edematous response following phosgene exposure were generally not successful.