白细胞介素协同作用抗小鼠新型隐球菌感染

Synergistic Effect of Interleukin in Protecting Mice Against Infection Caused by Cryptococcus neoformans

[目的]观察白细胞介素 12(IL-12)和白细胞介素 18(IL-18)对新型隐球菌感染小鼠细胞因子的影响和疗效.[方法]将(BALB/ c× DBA/ 2)小鼠 88只制成小鼠新型隐球菌感染模型后,随机分成 IL-12组、 IL-18组、 IL-12+ IL-18组和对照组(用磷酸缓冲液处理 ),每组 22只.根据处理方法治疗,检测肺泡灌洗液 IFN-γ、 IL-4、 IL-10含量(ELISA法 )和肺脑菌落计数,观察治疗后生存率.[结果]对照组、 I12组和 I18组小鼠全部死亡, IL-12+ IL-18组 4只死亡.肺菌落计数对照组(3 417± 1 177)× 108CFU/ L, IL-12组(3 914± 2 178)× 108 CFU/ L, IL-18组(3 416± 1 574)× 108 CFU/ L, IL-12+ IL-18组(500± 260)× 108CFU/ L.脑菌落计数对照组(21± 6)× 108CFU/ L, IL-12组(15± 5)× 108 CFU/ L, IL-18组(16± 8)× 108CFU/ L, IL-12+ IL-18组(2± 1)× 108CFU/ L.使用组 IFN-γ水平显著升高, IL-4和 IL-10水平下降,与对照组比较差异有显著性.[结论]IL-12和 IL-18协同诱导 IFN-γ产生,促进 Th1细胞反应,抑制 Th2细胞反应,改变了 Th1/ Th2平衡,对新型隐球菌感染小鼠产生保护效应.

[Objective] To study the effect of IL-12 and IL-18 on cytokines of murine infection with Cryptococcus neoformans. [Methods]88 (BALB/c ×DBA/2)mice infected with Cryptococ-cus neoformans. were randomized into IL-12, IL-18, IL-12 + IL-18 and normal control (PBS) (n = 22) groups, treated with PBS, IL-12 and/or IL-18 respectively. Level of IFN-y, IL-4 and IL-10 in bronchoalveolar lavage fluid were detected with ELISA method. The numbers of viable fungi in lung and brain were counted. Survival rate after treatment was investigated. [Results] In control, IL-12 and IL-18 groups, all mice were dead. In IL-12 + IL-18 group, 4 were dead. The numbers of viable fungi in lung were (3 417 ±1 177) ×108 CFU/L in control group, (3 914 ±2 178) × 108 CFU/L in IL-12 group, (3 416 ± 1 574) ×108 CFU/L in IL-18 group and (500 ±260) × 108 CFU/L in IL-12 + IL-18 group. The numbers of viable fungi in brain were (21 ±6) × 108 CFU/ L in control group, (15 ±5) × 108 CFU/L in IL-12 group, (16 ±8)× 108 CFU/L in IL-18 group, (2±1)×l08 CFU/L in IL-12 + IL-18 group. The level of IFN-y was increase, IL-4 and IL-10 was decrease in IL-12 + IL-18 group. There was significant difference between the combined group and the control group. [Conclusions] Combined treatment with IL-12 and IL-18 synergistic induced IFN-y production, promoted development of Thl cell responses, suppressed Th2 cell responses, modulated Thl and Th2 cytokine balance, suggesting that IL-12 + IL-18 enhance the host defense against pulmonary and disseminated infection caused by Cryptococcus neoformans.