]DOWN-REGULATION OF TRANSFORMING-GROWTH-FACTOR-BETA AND INTERLEUKIN-10 SECRETION FROM MALIGNANT GLIOMA-CELLS BY CYTOKINES AND ANTICANCER DRUGS

The effect of treatment with interleukin-1 beta (IL-1 beta), interfero n-gamma (IFN-gamma), vincristine, and etoposide was evaluated on the s ecretion of transforming growth factor-beta (TGF-beta) and IL-10 and t he expression of major histocompatibility complex (MHC) class I, inter cellular adhesion molecule-1 (ICAM-1), and CD80 molecules by malignant glioma cells. Five malignant glioma cell lines were treated with IL-1 beta, IFN-gamma, and/or anticancer agents (vincristine and etoposide) . Combined treatment with IL-1 beta and IFN-gamma caused greater inhib ition of TGF-beta secretion compared to treatment with IFN-gamma, and almost the same levels of inhibition as treatment with vincristine and etoposide. The greatest inhibition of TGF-beta secretion was achieved by treatment with all agents. Low levels of IL-10 secretion were dete rmined in two out of five malignant glioma cell lines. This IL-10 secr etion was inhibited by treatment with IL-1 beta, IFN-gamma, vincristin e, and/or etoposide. Treatment with both cytokines and anticancer agen ts increased the expression of MHC class I and ICAM-1 in all tumor cel l lines. The mean increase of expression of MHC class I was 50% and th at of ICAM-1 was 12-fold. No tumor cell lines expressed CD80 molecules on the cell surface, and no treatment caused CD80 expression. These r esults suggest that TGF-beta and IL-10 secretion by malignant glioma c ells can be suppressed by treatment with a combination of IL-1 beta, I FN-gamma, vincristine, and etoposide, and the treatment up-regulates M HC class I and ICAM-1 expression on tumor cells. These results have im plications for immunotherapy and chemotherapy in patients with maligna nt tumors.