The effect of recombinant cytokines on bladder cancer cells in vitro.

We have studied the Major Histocompatibility Class II-modulating and antiproliferative actions of recombinant interferon-gamma, tumor necrosis factor-alpha, interleukin-1 alpha, interleukin-2 and granulocyte macrophage-colony stimulating factor on bladder cancer cells in vitro. Indirect immunofluorescent staining employing monoclonal antibody probes in conjunction with flow cytometric analysis and tritiated thymidine incorporation assays were used. Interferon-gamma was a strong inducer and enhancer of class II antigens. Tumor necrosis factor-alpha could not induce the expression of class II antigens on tumor cells, which were initially class II-negative, but enhanced the expression on cells which already demonstrated low levels of the antigen. Interleukin-1, interleukin-2 and granulocyte macrophage-colony stimulating factor did not affect the major histocompatibility class II expression. Interferon-gamma and tumor necrosis factor-alpha both demonstrated powerful anti-proliferative effects on the bladder cancer cells, particularly those derived from low grade tumors (G1 and G2). Interleukin-1 alpha had no effect on tumor cell proliferation. In contrast interleukin-2 and granulocyte macrophage-colony stimulating factor had significant stimulatory effects on the proliferation of the low grade tumor cells (G1).