CYTOKINE PRODUCTION BY THE HUMAN BLADDER-CARCINOMA CELL-LINE T24 IN THE PRESENCE OF BACILLUS-CALMETTE-GUERIN (BCG)

The study was initiated as an in vitro approach to the situation exist ing during intravesical bacillus Calmette-Guerin (BCG) instillation in patients with superficial bladder cancer. Cytokine secretion of a hum an bladder carcinoma cell line T 24 treated with BCG was investigated. A 24-h treatment of T24 cells with BCG resulted in a tenfold higher s ecretion of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFa lpha) when compared with T24 cells treated with Escherichia coli, Stre ptococcus faecalis or a cell wall preparation of Nocardia rubra (N-CWS ). No secretion of IL-1beta and IL,2 was detected. Pre-exposing T24 ce lls to BCG for various periods of time indicated that a minimum exposu re time of 0.5 - 1 h was required to upregulate IL-6 and TNFalpha prod uction. Extending the BCG pre-exposure time to 2 and 3 h further incre ased the rate of cytokine production. No significant difference was fo und, however, between the rate of secretion initiated after a 2-h or 3 -h pre-exposure period. The amounts of these cytokines secreted in the presence of BCG-conditioned medium did not differ significantly from the constitutively secreted amounts, excluding an effect of products p ossibly secreted by BCG on the upregulation of IL-6 and TNFalpha. In a ddition, upregulation of cytokine production appeared to be dependent on the concentration of BCG. The results suggest that cytokines may be produced by urothelial tumor cells after intravesical instillation in patients with superficial bladder cancer, which may play a role in th e mode of action of BCG.