In Vivo Induction of Gamma Interferon and Tumor Necrosis Factor by Interleukin - 2 Infusion Following Intensive Chemotherapy or Autologous Marrow

lnterleukin-2 (11-2) therapy may improve immune reconstitution and reduce the risk of leukemic relapse in the setting of minimal residual disease by augmenting cytotoxic effector mechanisms directed at residual malignant cells. In addition. 11-2 in vitro promotes the release of cytokines including y-interferon (‘y-IFN) and tumor necrosis factor (TNF). which also possess antileukemic activity and can enhance granulocyte function. To determine if 11-2 infusion induces release of ‘y-IFN and TNF in vivo in sufficient quantity to mediate these effects. we have measured serum levels of these cytokines and secretion by lymphocytes obtained from patients receiving this cytokine in a phase 1 trial. Serum ‘y-IFN was undetectable pre-IL-2 and increased to 1 .5 to 1 7 U/mI during 11-2 infusion (P < .05). Culture of patient lymphocytes for 48 hours produced 1 .2 U ‘y-IFN/2 x 10 cells/mi pre-lL-2 rising to 50 U/2 x 10’ cells/mi when the lymphocytes were obtained during therapy (P < .05). iymphocyte subset analysis showed that both CD3 + and CD1 6 + cells secreted ‘y-IFN in