The effect of various cytokines on the in vitro induction of antibody-dependent cellular cytotoxicity in murine cells. Enhancement of IL-2-induced antibody-dependent cellular cytotoxicity activity by IL-1 and tumor necrosis factor-alpha.
We have previously demonstrated that incubation with IL-2 can induce ADCC activity in murine cells and that this activity was mediated by asialo GM1+, FcR+ cells. In the present study we show that the cytokines IFN-alpha and IFN-gamma, TNF-alpha, and IL-1 alpha are unable to induce antibody-dependent cellular cytotoxicity (ADCC) in murine cells; however, TNF-alpha and IL-1 alpha could substantially augment the ADCC induced by IL-2. IL-1 increased the IL-2-induced ADCC activity in a dose-dependent fashion and in cells isolated from the thymus and spleen. The precursors of the ADCC induced by the combination of IL-1 and IL-2 were asialo GM1+ cells, similar to the precursor cells of IL-2-induced ADCC. The effect of IL-1 and TNF on ADCC was not the result of an increase in the FcR density on the cell surface or the result of an increase in the number of FcR+ cells although IL-1 increased the recovery of viable cells in culture. The main effect of IL-1 and TNF was the enhancement of the lytic ability of the IL-2 cultured cells as indicated by increased intra-cellular benzyloxycarbonyl L-lysine thiobenzylester-esterase activity. These results suggest that lymphokines such as IL-1 and TNF may synergize with IL-2 in the induction of ADCC and could thus potentially be useful for the immunotherapy of established tumors when combined with the administration of specific anti-tumor antibodies.
Eisenthal
A
A
Surgery Branch, National Cancer Institute, Bethesda, MD 20892.
Rosenberg
S A
SA
D000818:Animals; D000920:Antibody-Dependent Cell Cytotoxicity / Q000187:drug effects*; D001685:Biological Factors / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines; D004306:Dose-Response Relationship, Immunologic; D004338:Drug Combinations; D005260:Female; D005677:G(M1) Ganglioside; D006028:Glycosphingolipids; D053804:Granzymes; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010641:Phenotype; D011961:Receptors, Fc; D012697:Serine Endopeptidases / Q000378:metabolism; D013601:T-Lymphocytes / Q000145:classification / Q000201:enzymology / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D001685:Biological Factors; D016207:Cytokines; D004338:Drug Combinations; D006028:Glycosphingolipids; D007375:Interleukin-1; D007376:Interleukin-2; D011961:Receptors, Fc; D014409:Tumor Necrosis Factor-alpha; D005677:G(M1) Ganglioside; C018835:asialo GM1 ganglioside; D053804:Granzymes; D012697:Serine Endopeptidases