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

Purpose: To determine the effects of live BCG, autoclaved BCG and interfero n alpha-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 assa y. The mRNA level of IL-6 and GM-CSF was determined by RT-PCR. Results: BCG and/or interferon alpha-2b differentially increased IL-1 beta, IL-6, IL-8, GM-CSF and TNF-alpha production in the bladder cancer cells. H igh grade cell lines were more responsive to BCG whereas low grade lines we re more sensitive to interferon alpha-2b. This correlated with cytotoxicity and growth inhibition induced by these agents. BCG could also induce low l evels of IFN-alpha production in all the cell lines. Compared with live BCC , 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 stimul ating IL-6 and TNF-alpha production of J82 cells. The combination of BCG an d interferon alpha-2b also completely suppressed TGF-beta 1 production in t he MGH and RT112 cell lines. Conclusions: The combination of BCG and interferon alpha-2b has additive ef fects in cytokine production from bladder cancer cells. This correlates wit h cytotoxicity and growth inhibition induced by these agents.