Shin J S, Park J H, Kim J D, Lee J M, Kim S J
Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea.
Clin Exp Immunol. 1995 Apr;100(1):26-31. doi: 10.1111/j.1365-2249.1995.tb03599.x.
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-alpha in spleens and bladders of mice after intravesical BCG or BCG/interferon-gamma (IFN-gamma) instillation. Significant change of TNF-alpha mRNA expression of spleens and bladders of C3H/He mice was observed after intravesical BCG instillation, although intravesical IFN-gamma therapy 3 days after BCG instillation to maintain the activated state of monocyte/macrophage lineage cells did not show a significant change of TNF-alpha mRNA, compared with that of BCG therapy alone. Maximal production of TNF-alpha mRNA in spleens of mice was seen after the first or second intravesical BCG instillation, and production of TNF-alpha mRNA in bladders was also increased after intravesical BCG instillation. The increment of TNF-alpha 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-alpha as well as systemic production by intravesical BCG treatment may correlate with one of the mechanisms of BCG immunotherapy of superficial bladder cancer.
膀胱内灌注卡介苗（BCG）疗法在膀胱原位癌的治疗中非常有效，但BCG免疫疗法的机制尚不清楚。我们研究了膀胱内灌注BCG或BCG/γ干扰素（IFN-γ）后小鼠脾脏和膀胱中肿瘤坏死因子-α（TNF-α）的产生情况。膀胱内灌注BCG后，观察到C3H/He小鼠脾脏和膀胱中TNF-α mRNA表达有显著变化，尽管在BCG灌注3天后进行膀胱内IFN-γ治疗以维持单核细胞/巨噬细胞系细胞的激活状态，但与单独BCG治疗相比，TNF-α mRNA没有显著变化。在首次或第二次膀胱内灌注BCG后，小鼠脾脏中TNF-α mRNA产生最多，膀胱内灌注BCG后膀胱中TNF-α mRNA的产生也增加。在体外，BCG刺激早幼粒细胞白血病细胞系HL-60和外周血单个核细胞产生TNF-α的增加可能支持BCG疗法对膀胱的体内作用。这些数据表明，膀胱内BCG治疗引起的TNF-α局部产生以及全身产生可能与浅表性膀胱癌BCG免疫疗法的机制之一相关。
