为了研究白细胞介素-18(IL-18)基因对人免疫缺陷病毒(HIV-1)核酸疫苗诱导免疫应答的影响，将人IL-18基因插入到真核表达载体pVAX1中，构建了真核表达载体pVAX1-IL-18；将pCI-neoGAG联合pVAX1-IL-18或者pCI-neoGAG单独免疫Balb/c小鼠，检测免疫小鼠的特异性抗体和IFN-γ，同时观察免疫小鼠脾淋巴细胞增殖和小鼠特异性细胞毒性T淋巴细胞(CTL)反应。酶切及测序结果表明成功地构建了人IL-18基因真核表达载体；与pCI-neoGAG免疫组比较，pCI-neoGAG联合pVAX1-IL-18免疫组小鼠血清的抗HIV-1p24抗体滴度降低（P0.01）；而与pCI-neoGAG免疫组比较，pCI-neoGAG联合pVAX1-IL-18免疫组小鼠血清的IFN-γ升高（P0.01）；pCI-neoGAG联合pVAX1-IL-18免疫组小鼠的脾淋巴细胞增殖实验刺激指数（SI）以及特异性CTL 活性均高于pCI-neoGAG免疫组（P0.01）。IL-18基因联合HIV-1核酸疫苗免疫小鼠，可能增强特异性Th1细胞和CTL反应，白细胞介素-18基因对体液免疫有抑制作用。

To investigate the effect of interleukin-18 (IL-18) DNA immunization on immune response induced by Human immunodeficiency virus 1(HIV-1) nucleic acid vaccine (DNA vaccine), the recombinant expression vector pVAX1-IL-18 was constructed by inserting the IL-18 gene into the eukaryotic expression vector pVAX1. Balb/c mice were immunized with pCI-neoGAG alone or co-administered with the DNA encoding for IL-18. Their sera were collected for analyzing anti-HIV antibody and IFN-γ by ELISA, and spleen cells were isolated for detecting antigen-specific lymphoproliferative responses and specific CTL response by MTT assay and LDH assay, respectively. Restriction enzymes digestion analysis and DNA sequencing results revealed that the recombinant expression vector pVAX1-IL-18 has been constructed successfully. The anti-HIV antibody titers of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-18 were lower than that of mice immunized with pCI-neoGAG alone (P0.01). In contrast, the IFN-γ level of mice co-immunized with pCI-neoGAG and the DNA encoding for IL-18 was higher than that of mice immunized with pCI-neoGAG alone (P0.01). Furthermore, compared with mice injected with pCI- neoGAG alone, the specific CTL cytotoxity and antigen-specific lymphoproliferative responses of mice immunized with pCI-neoGAG and the DNA encoding for IL-18 were significantly enhanced (P0.01). The DNA encoding for IL-18 together with HIV DNA vaccine may enhance specific Th-1 responses and cellular immune responses elicited in mice. However, the DNA encoding for IL-18 may down-regulate the humoral responses.