Cytotoxic Effect of BCG on Tumor Cells Viewed in Cytokine Activities Induced in Vitro

Abstract

The present study was designed to investigate the relationship between the efficacy of the BCG instillation therapy, cytokine production of peripheral blood mononuclear cells (PBMC) activated by BCG in vitro, and the concentration of cytokines in serum and urine following BCG instillation. We studied 7 patients who had carcinoma in situ of the urinary bladder. Tokyo strain 172 BCG was administered weekly for 8 weeks as 80 mg of BCG in 40 ml of saline, instilled into the bladder and retained for 2 hours. Out of the 7 patients, 6 achieved complete remission after 8 sessions of instillation. In 5 of the 7 patients, cytokine production by PBMC after incubation with BCG in vitro was studied. After co-culture of BCG and PBMC for 24 hours, concentrations of TNF alpha and IFN gamma in the supernatant ranged from 216 to 3563 pg/ml (mean; 1146 ± 1384), from 992 to 2030 pg/ml (mean; 1398 ± 487), respectively. Although concentrations of TNF alpha in serum were slightly elevated in 3 of 7 and IFN gamma in 1 of 7 patients at 6 hours following the first session of BCG instillation, concentrations of these cytokines in the urine were not elevated. There was no relationship between the tumor response to BCG therapy, concentrations of TNF alpha or IFN gamma in serum and urine, and the concentration of cytotoxic cytokines mediated by BCG in vitro.