Serum concentration kinetics of γ-interferon (IFN-γ), neopterin, 2′-5′A synthetase and tumor necrosis factor α 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-γ and tumor necrosis factor α.
After IL-2 bolus injection, the kinetics of neopterin was similar but delayed when compared to that of IFN-γ: this suggests that macrophages, the specific source of neopterin, become activated by IFN-γ following IL-2-mediated lymphocyte induction, thus implying a possible role for macrophages in the antitumor effects mediated by IL-2 and lymphokineactivated killer cells.
This study was supported by a grant from Istituto Superiore di Sanità, Rome, Italy (“Italy-USA Project on Therapy of Tumors”).