Adoptive immunotherapy of human cancer: the cytokine cascade and monocyte activation following high-dose interleukin 2 bolus treatment

Abstract

Serum concentration kinetics of gamma-interferon (IFN-gamma), neopterin, 2'-5' A synthetase and tumor necrosis factor alpha were determined in five cancer patients undergoing adoptive immunotherapy with high-dose interleukin 2 (IL-2) bolus infusion and lymphokine-activated killer cells according to the National Cancer Institute, NIH protocol. In all cases a significant increase of these markers was observed after IL-2 treatment. This suggests that the antitumor effect of high-dose IL-2 bolus administration may be in part mediated by activation of a cascade of endogenous cytokines including IFN-gamma and tumor necrosis factor alpha. After IL-2 bolus injection, the kinetics of neopterin was similar but delayed when compared to that of IFN-gamma: this suggests that macrophages, the specific source of neopterin, become activated by IFN-gamma following IL-2-mediated lymphocyte induction, thus implying a possible role for macrophages in the antitumor effects mediated by IL-2 and lymphokine-activated killer cells.