Induction of tumour necrosis factor-alpha (TNF-α) mRNA in bladders and spleens of mice after intravesical administration of bacillus Calmette-Guérin

Abstract

SUMMARY Intravesical bacillus Calmette Guérin (BCG) therapy is highly effective in the therapy of carcinoma in situ of the bladder, but the mechanism of BCG immunotherapy is not clearly understood. We studied the production of TNF-n in spleens and bladders of mice after intravesical BCG or BCG/interferon-gamma (IFN-γ) instillation. Significant change of TNF-a mRNA expression of spleens and bladders of C3H/He mice was observed after intravesical BCG instillation, although intravesical IFN-γ therapy 3 days after BCG instillation to maintain the activated state of monocyte/ macrophage lineage cells did not show a significant change of TNF-α mRNA, compared with that of BCG therapy alone. Maximal production of TNF-α mRNA in spleens of mice was seen after the first or second intravesical BCG instillation, and production of TNF-α mRNA in bladders was also increased after intravesical BCG instillation. The increment of TNF-α production by BCG stimulation in HL-60, a promyelocytic leukaemic cell line, and peripheral blood mononuclear cells in vitro may support the in vivo effect of BCG therapy on the bladder. These data show that local production of TNF-a as well as systemic production by intravesical BCG treatment may correlate with one of the mechanisms of BCG immunotherapy of superficial bladder cancer.