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

• Published in: The Journal of immunology (1950) Vol. 142; no. 7; pp. 2307 - 2313
• Main Authors: Eisenthal, A, Rosenberg, SA
• Format: Journal Article
• Language: English
• Published: United States Am Assoc Immnol 01.04.1989
• Subjects: Animals; Antibody-Dependent Cell Cytotoxicity - drug effects; Biological Factors - pharmacology; Cells, Cultured; Cytokines; Dose-Response Relationship, Immunologic; Drug Combinations; Female; G(M1) Ganglioside; Glycosphingolipids; Granzymes; Interleukin-1 - pharmacology; Interleukin-2 - pharmacology; Lymphocyte Activation; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Inbred DBA; Phenotype; Receptors, Fc; Serine Endopeptidases - metabolism; T-Lymphocytes - classification; T-Lymphocytes - enzymology; T-Lymphocytes - immunology; Tumor Necrosis Factor-alpha - pharmacology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.142.7.2307

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.