In vitro modulation of cisplatin resistance by cytokines.

We have previously demonstrated that treatment of wild-type (wt) T98G malignant glioma cells with Cisplatin (CDDP) led to a resistant phenotype. It has been demonstrated that interleukin 1 (IL-1) potentiates the cytotoxic effect of CDDP and that IL-6 decreases cytotoxicity by inhibition of apoptosis in cancer cells. Here we examined the influence of IL-1 and IL-6 on the sensitivity of resistant and wt T98G cells. Using semi-quantitative PCR reactions in three independent experiments, resistant glioma cells revealed a decreased IL-1alpha (50.3+/-7.2), IL-1beta (56.0+/-4.0) and IL-6 (44. 3+/-18.2) mRNA content compared to wt cells (100%;P<0.05). Resistant and wt cells were positive for the receptors IL-1RI and IL-6R (PCR). To investigate whether IL-1alpha, IL-1beta or IL-6 changes the sensitivity of the resistant and wt cells towards CDDP, cells were incubated up to 7 days with 10(-5) M CDDP and with different concentrations (0, 0.01, 0.1, 1 ng/ml) of cytokine. Sensitivity was tested in a colorimetric assay (MTT). IL-6 did not influence the sensitivity towards CDDP of either wt or resistant cells, while IL-1alpha and IL-1beta enhanced sensitivity of resistant cells to CDDP. These data suggest that autocrine IL-1 production is involved in the mechanisms of resistance in T98G cells.