CHARACTERIZATION OF THE PULMONARY-LESIONS INDUCED IN RATS BY HUMAN RECOMBINANT INTERLEUKIN-2

Histologic, electron microscopic, and immunohistochemical studies were made to analyze the structural features and the cellular composition of the pulmonary lesions produced in rats by the administration of int erleukin-2 (IL-2). This agent induced pulmonary edema; thickening of a lveolar septa; damage to endothelial cells in capillaries and venules, marked interstitial infiltration by cytotoxic T lymphocytes, lymphoki ne-activated killer (LAK) cells, macrophages, and dendritic cells (as demonstrated by cell counting in preparations stained immunohistochemi cally with peroxidase- and fluorochrome-labeled antibodies); and injur y to bronchiolar and alveolar epithelial cells. Granular and agranular lymphocytes often were closely apposed to endothelial cells in capill aries and venules. Contacts between lymphocytes and type II alveolar e pithelial cells also were observed. Damaged type II alveolar epithelia l cells showed nuclear and cytoplasmic features that are considered in dicative of apoptosis (confirmed by nick end labeling). Phagocytosis o f apoptotic bodies by macrophages was occasionally found. These result s support the concept that IL-2 induces cytotoxic vascular and parench ymal cell damage that is mediated by LAK cells and cytotoxic T lymphoc ytes, which make contacts with endothelial cells and type II alveolar epithelial cells. This damage appears to be exacerbated by the seconda ry release of a variety of vasoactive agents and inflammatory mediator s.