INTERLEUKIN-2 DOES NOT SEQUESTER ACTIVATED LYMPHOCYTES INTO LUNG LYMPH OF SHEEP

Purpose of study:Interleukin-2 (IL-2) is a potent activator of lymphoc ytes, but its effectiveness as an anticancer agent is compromised by s everal adverse side effects including pulmonary edema. One explanation for the pulmonary toxicity of IL-2 is that activated lymphocytes dire ctly induce the pulmonary vascular endothelium to become more leaky, M ethods: To test this hypothesis the number of total lymphocytes, gamma delta T cells, and CD2-positive cells (alpha beta T cells and natural killer cells) in peripheral blood and lung lymph of sheep were compar ed before and after IL-2 infusion. Hemodynamic and lymph dynamic chang es were also evaluated. Results: IL-2 decreased mean aortic pressure, increased cardiac output, lowered systemic vascular resistance, and do ubled lung lymph flow (P less than or equal to 0.05), but had no effec t on plasma or lymph oncotic pressure. The lymph protein concentration and the lymph-to-plasma protein concentration ratio were not differen t after IL-2 infusion. IL-2 had no effect on the number of total lymph ocytes, gamma delta T cells, or CD2-positive cells in the peripheral b lood. In contrast, the number of total lymphocytes, gamma delta T cell s, and CD2-positive cells in lung lymph decreased significantly (P les s than or equal to 0.05), Conclusions: The lymphocyte populations decr eased more than could be explained by the increase in lymph flow, demo nstrating that lung lymphocytes were not reduced simply by dilution. T hese results imply that the pulmonary edema associated with IL-2 is no t caused by activated lymphocytes. (C) 1996 Academic Press, Inc.