The administration of large amounts of interleukin-2 (IL-2) to patients with cancer produces a vascular leak syndrome and myocarditis. We have developed an animal model for this study of this toxicity in rats. In these animals, IL-2 induced myocarditis characterized by: infiltration of the myocardium by lymphocytes, macrophages, eosinophils and neutrophils; damage to endothelial cells in the venules and capillaries, and myocyte damage and necrosis. The microvascular lesions appeared to result from the contacts between activated endothelial cells and activated lymphocytes (which had been induced by IL-2 to become lymphokine-activated killer cells or LAK cells). Myocyte lesions were attributed to two factors: microcirculatory disturbances and cytolytic damage associated with contacts between activated lymphocytes and myocytes.
