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Toxicologic Pathology
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Journal Article

Characterization of the Pulmonary Lesions Induced in Rats by Human Recombinant Interleukin-2

Jun Zhang

Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1518, Division of Research and Testing, Food and Drug Administration (HFD-472), Laurel, Maryland 20708

Robert J. Wenthold, JR.

Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1518

Zu-Xi Yu

Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1518

Eugene H. Herman

Division of Research and Testing, Food and Drug Administration (HFD-472), Laurel, Maryland 20708

Victor J. Ferrans

Pathology Section, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892-1518

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 interleukin-2 (IL-2). This agent induced pulmonary edema; thickening of alveolar septa; damage to endothelial cells in capillaries and venules, marked interstitial infiltration by cytotoxic T lymphocytes, lymphokine-activated killer (LAK) cells, macrophages, and dendritic cells (as demonstrated by cell counting in preparations stained immunohistochemically with peroxidase- and fluorochrome-labeled antibodies); and injury to bronchiolar and alveolar epithelial cells. Granular and agranular lymphocytes often were closely apposed to endothelial cells in capillaries and venules. Contacts between lymphocytes and type II alveolar epithelial cells also were observed. Damaged type II alveolar epithelial cells showed nuclear and cytoplasmic features that are considered indicative of apoptosis (confirmed by nick end labeling). Phagocytosis of apoptotic bodies by macrophages was occasionally found. These results support the concept that IL-2 induces cytotoxic vascular and parenchymal cell damage that is mediated by LAK cells and cytotoxic T lymphocytes, which make contacts with endothelial cells and type II alveolar epithelial cells. This damage appears to be exacerbated by the secondary release of a variety of vasoactive agents and inflammatory mediators.

Key Words: Lymphokine-activated killer cells • cytotoxic T lymphocytes • interstitial dendritic cells • endothelial cells • pulmonary pathology • type II alveolar epithelial cells • apoptosis

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Toxicologic Pathology, Vol. 23, No. 6, 653-666 (1995)
DOI: 10.1177/019262339502300603
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