细胞因子对小鼠结核分枝杆菌感染的免疫保护作用

Immuno-protection Efficacy of Cytokines Against TB in Mice

目的研究细胞因子IFN-γ和TNF对小鼠结核分枝杆菌感染的免疫保护作用。方法小鼠结核分枝杆菌感染后第5 d给予IFN-γ和/或TNF治疗,观察治疗后半数死亡时间、一定时间内的死亡率、脾内活菌数,检测脾细胞分泌IFN-γ和IL-4水平(ELISA法)及MΦ产生NO水平(用Griess试剂)。结果IFN-γ和TNF联用组与单纯攻毒组比较明显延长感染小鼠半数死亡时间、降低感染小鼠35 d内的死亡率、显著减少感染小鼠脾内活菌数,脾细胞IFN-γ分泌水平明显升高,IL-4分泌水平显著降低,MΦ产生NO水平明显增加。结论IFN-γ和TNF联合诱导MΦ产生NO,促进Th1细胞反应,抑制Th2细胞反应,改变了Th1/Th2平衡,对小鼠结核分枝杆菌感染产生保护效应。

Objective To study the immuno-protectlve efficacy of IFN-γ combined with TNF against mycobacterium tuberculosis infected mice. Methods The mice were treated with IFN-γ and /or TNF for 5 days postinfection challenged with H27Rv by their tail veins. Time of fifty percent death （T50） and mortality rate within 35 days were investigated. The numbers of viable bacteria in spleen were counted. The level of IFN-γ and IL-4 in ConA-indueed spleen cell cultural supernatant were detected with enzyme linked immunosorbent assay （ELISA） method. The level of nitric oxide （NO） in macrophage cultural supernatant was measured using Griess reagent. Results The combination of IFN-γ with TNF group prolonged T50,decreased mortality rate within 35 days,diminished the numbers of viable bacteria in spleen,promoted the level of IFN-γ and reduced the level of IL-4 secreted by spleen cells ,enhanced the production of NO secreted by MΦ. There was significant difference compared with infection control group （P〈0. 01）. Conclusion The combination of IFN-γ with TNF could induce NO production by MΦ,promote development of Th1 cell response,inhibit Th2 cell response,modulate Th1 and Th2 cytokine balance,which suggested that could enhance the host defense against the infection with H27Rv.