高危型人乳头状瘤病毒和Th细胞因子与宫颈病变的关系及意义

Relationship and clinical significance between T helper cell and cervical lesions among patient with high risk of HPV infection

目的比较高危型人乳头状瘤病毒(HPV)持续性感染所致不同程度的宫颈病变,分析T辅助细胞(Th)在此演变过程中的作用,明确抗HPV感染免疫应答和抗病毒细胞因子在疾病转归中的重要调节机制。方法对86例高危型HPV16/18阳性的患者依所致宫颈病变的不同分为5组,CIN I、CIN II、CIN III,宫颈癌和宫颈炎,检测其INF-γ、TNF-α、IL-10、IL-5、IL-4、IL-2水平,采用方差分析和多元线性回归,分析不同病变患者6种细胞因子的水平差异,及其每个细胞因子对病变程度的影响。结果在宫颈炎、CIN I、CIN II表现为Th 1优势,CIN III和宫颈癌表现为Th 2优势;宫颈炎、CIN I病变组,IL-2、INF-γ、TNF-α均有升高,CIN II仅有IL-2升高。比较回归方程中的标准偏回归系数,对宫颈病变影响程度依次为INF-γ>TNF-α>IL-2>IL-10。结论在抗HPV持续感染免疫应答中,Th 1优势更利于机体清除病毒,Th1向Th2的偏移,可加重宫颈病变。细胞因子对该过程有重要的调节作用,一方面上调或下调免疫反应,增强或抑制免疫应答,另一方面直接作为抗病毒的效应分子发挥作用。

Objective To compare the different degrees of cervical lesions induced by persistent infection of high risk HPV,and analysis the effect of T helper cell during the course of the evolution process,in order to definite the very important regulation mechanismof HPV infect-resistant immunity response and antiviral cytokines in the disease development. Methods 86 positive highrisk HPV16 and 18 patients were divided into five groups based on the difference of cervical lesions,including CINⅠ,CINⅡ,CINⅢ,cervical cancer and cervicitis. The levels of serum interferon-γ（ IFN-γ）,tumor necrosis factor-α（ TNF-α）,interleukin-10（ IL-10）,interleukin-5（ IL-5）,interleukin-4（ IL-4）,interleukin-2（ IL-2） were measured. Then the results were compared and analyzed by the variance analysis and the multiple linear regressions. Results In CIN Ⅰ,CIN Ⅱ and cervicitis groups,the patients showed Th1 dominance,while CINⅢ and cervical cancer groups existed Th2 dominance. IL-2,INF-γ,TNF-α levels in CIN Ⅰ and cervicitis groups all increased,however,only IL-2 levels increased in CINⅡ group. The impact on cervical lesions was in sequence of INF-γ TNF-α IL-2 IL-10. Conclusion During the course of the HPV infect-resistant immunity response,Th1 dominance is more beneficial to eliminating virus,so cervical lesions may aggravate due to Th1 / Th2 cells drift. Cytokine can up-regulate or down-regulated the immune response,on the other side it can also play a direct role of the antivirus action.