Secretion and production of reactive nitrogen intermediates in urine and peritoneal macrophages after intravesical BCG instillation in the rat / 대한비뇨기과학회지

ABSTRACT

Cells or the monocyte-macrophage lineage are known to exhibit tumoricidal activity following stimulation by BCG, interferon -gamma (INF-gamma) or bacterial products such as lipopolysaccharide(LPS). While the mechanisms involved remain obscure, the generation of reactive nitrogen intermediateds (RNI) by activated macrophage is considered a major participant in mediating the tumoricidal effect. In this study, the authors intended to know the effects of BCG infection on the production and secretion of RNI in the experimental animals. Sprauge-Dawley rats were instillated with BCG intravesically. The production of RNI from peritoneal macrophages and urinary secretion of RNI were measured after intravesical BCG instillation of the rats. The urinary concentration(micrometer/L) of nitrite, stable oxidized form of nitric oxide(N0-), 1 week after intravesical BCG instillation was 20+/-0.5 in the group I (control). 54+/-1.0 in group II (BCG 1x). 63+/-0.5 in group III (BCG 10x) and 17+/-0.5 in group IV (BCG 10x + N(G)MMA). The urinary nitrite concentration(micrometer/L) 3 weeks after intravesical BCG instillation was 17+/-2.0 in group I, 124+/-3.0 in group II, 210+2.5 in group III and 31+/-0.5 in group IV. The production of RNI by peritoneal macrophages 3 weeks after intravesical BCG instillation increased in group III (45+/-2.0 micrometer/L) compared to group I (5+/-1.0 micrometer/L). The peritoneal macrophages treated with LPS and INF-gamma increased nitrite production (36+/-0.5 in group I , 52+/-1.5 micrometer/L in group III). The production of RNI by peritoneal macrophages was inhibited by the treatment of the rats with N(G)MMA (19+/-0.5 in group 1, 17+/-1.5 micrometer/L in group III). The results of this study showed that BCG infection of the rat via intravesical instillation makes the peritoneal macrophages produced RNI and increases the secretion of RNI in the urine. This study suggest that the effects of BCG infection for the treatment of bladder cancer might be mediated by the production or RNI in the tumor bearing host.