Effects of bacillus Calmette-Guerin and interferon α-2b on cytokine production in human bladder cancer cell lines

Abstract

Purpose: To determine the effects of live BCG, autoclaved BCG and interferon α-2b on cytokine production in human bladder cancer cell lines. Materials and Methods: The release of nine cytokines from the human bladder cancer cell lines, RT4, RT112, SD, MGH and J82, was measured by ELISA assay. The mRNA level of IL-6 and GM-CSF was determined by RT-PCR. Results: BCG and/or interferon α-2b differentially increased IL-1β, IL-6, IL-8, GM-CSF and TNF-α production in the bladder cancer cells. High grade cell lines were more responsive to BCG whereas low grade lines were more sensitive to interferon α-2b. This correlated with cytotoxicity and growth inhibition induced by these agents. BCG could also induce low levels of IFN-α production in all the cell lines. Compared with live BCG, autoclaved BCG had no antiproliferative effect on MGH cells and was less effective in stimulating the production of IL-6, IL-8 and GM-CSF. However, autoclaved BCG was as effective as live BCG in inhibiting growth and stimulating IL-6 and TNF-α production of J82 cells. The combination of BCG and interferon α-2b also completely suppressed TGF-β1 production in the MGH and RT112 cell lines. Conclusions: The combination of BCG and interferon α-2b has additive effects in cytokine production from bladder cancer cells. This correlates with cytotoxicity and growth inhibition induced by these agents.