全氟化合物与儿童哮喘及Th1/Th2免疫应答平衡相关性研究

目的 采用病例对照探讨全氟化合物(PFAAS)暴露与儿童哮喘及Th1型细胞因子白细胞介素(IL)-2,干扰素(IFN)-γ和Th2型细胞因子(IL-4,IL-5)分泌水平的关系.方法 选择231名台北医院就诊的哮喘儿童作为病例组,来自社区的225名自然儿童作为对照组.采用双抗体酶联免疫吸附实验(ELISA)试剂盒检测儿童血清中细胞因子IL-2、IFN-γ、IL-4和IL-10的分泌水平;高效液相色谱仪分析血清中全氟辛烷磺酸(PFOS)和全氟辛酸(PFOA)水平.结果 哮喘儿童机体PFOS(33.9μg/L比28.9 μg/L)和PFOA(1.2μg/L比0.5 μg/L)暴露负荷显著的高于对照组儿童,且随着机体PFAAs的增高,儿童患有哮喘的风险呈增高趋势.对哮喘儿童而言,血清PFAAs水平与Th1型细胞因子(IL-2,IFN-γ)存在显著的负相关,而与Th2型细胞因子(IL-4,IL-5)呈正相关关系.结论 PFOS暴露可诱导机体免疫应答平衡紊乱,并向Th2型免疫应答极化.

Effects of PFOS and PFOA exposure on asthma outcomes and the balance of Th1 and Th2 in children

Objective To assess the associations of serum polyfluoroalkyl substances (PFAAs) concentrations with increased odds of asthma and the levels of key Th2 cytokines in children.Methods A total of 231 asthmatic children from Taipei hospital and 225 non-asthmatic controls from seven schools of Taipei city were recruited in the genetic and biomarker study for Childhood Asthma.Serum concentrations of two PFAAs and levels of Th1 interferon (IFN)-γ,interleukin (IL)-12] and Th2 (IL-4 and IL-5) cytokines were also measured.The associations of PFAAs quartiles with the concentrations of immunological markers and asthma outcomes were estimated using multivariable regression models.Results The results showed that asthmatics had serum PFAAss values significantly higher than their healthy counterparts.Adjusted odds ratios for asthma among those with the highest versus lowest quartile of PFAAs exposure ranged from 2.63 (95％ CI:1.48,4.69) for the perfluorooctane sulfonate (PFOS) to 4.05 (95％ CI:2.21,7.42) for perfluorooctanic acid (PFOA).PFAAs were associated positively with serum Th2 cytokines and inversely with Th1 cytokines among asthmatics.However,among children without asthma,these associations were not significant.Conclusion The present study indicated that increased serum PFAAs levels may promote TH cell dysregulation and alter the availability of key Th1 and Th2 cytokines.These effects that could ultimately contribute to development of pulmonary allergic diseases.