白细胞介素12对结核病患者TH1/TH2平衡的影响

目的探讨白细胞介素12(IL-12)对结核病患者外周血单个核细胞(PBMC)分泌干扰素γ(IFN-γ)、白细胞介素4(IL-4)的影响.方法随机将25例结核患者和15名健康人PBMC分为RPMI1 640组、PPD组、PPD+rhIL-12组、PPD+anti-IL-12组,采用ELISA法检测各组培养上清液中IFN-γ、IL-4的水平.结果与PPD组相比,加入rhIL-12能有效增加结核患者及健康人PBMC分泌IFN-γ(分别为321.6±87.7至452.5±111.4, 387.0±70.8至515.4±44.1), 减少IL-4的分泌(54.6±11.0至41.3±13.5,55.1±9.5至38.2±12.7);而加入anti-IL-12可抑制IFN-γ的分泌,促进IL-4合成,且结核患者各组IFN-γ水平均低于健康人各对应组,而IL-4水平无差异.复治组IFN-γ、IL-4水平均低于初治组(P<0.05).结论 IL-12通过诱导IFN-γ分泌,抑制IL-4合成,从而调节TH1/TH2平衡,对结核分支杆菌感染患者产生保护性的免疫反应.IL-12可作为结核免疫调节剂,并可用于开发结核新疫苗.

The effect of interleukin-12 on the production of Th1 and Th2 cytokines by peripheral blood mononuclear cells from patients with tuberculosis

OBJECTIVE: To investigate the effect of IL-12 on the production of IFN-gamma and IL-4 by peripheral blood mononuclear cells (PBMC) from patients with tuberculosis. METHODS: PBMCs were isolated and cultured with RPMI 1640, PPD, PPD + rhIL-12, PPD + anti-IL-12, respectively. The level of IFN-gamma and IL-4 was detected with ELISA. RESULTS: Compared with the PPD group, IL-12 increased the production of IFN-gamma (321.6 +/- 87.7 vs 452.5 +/- 111.4, 387.0 +/- 70.8 vs 515.4 +/- 44.1, respectively), but decreased the production of IL-4 (54.6 +/- 11.0 vs 41.3 +/- 13.5, 55.1 +/- 9.5 vs 38.2 +/- 12.9, respectively) in the patients and the healthy individuals; anti-IL-12 blocked this effect. The level of IFN-gamma was lower in tuberculosis patients than that in the healthy controls. The IL-4 level was not different between the two groups (P > 0.05). The levels of IFN-gamma and IL-4 were lower in recurrent tuberculosis than those in the newly-diagnosed cases (P < 0.05). CONCLUSIONS: IL-12 induced IFN-gamma production and inhabited IL-4 expression, modulating the balance between TH(1) and TH(2) cytokines, suggesting that IL-12 enhances the host defense against tuberculous infection. IL-12 may be used for treatment of tuberculosis and vaccine development.