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目的在T细胞和单核细胞水平观察1α,25(OH)2D3对儿童桥本甲状腺炎(HT)TH1/TH2型细胞因子的影响,为1α,25(OH)2D3干预儿童HTTH1/TH2功能失衡提供理论依据。方法以2003-07—2004-08重庆医科大学儿童医院收治的27例HT患儿为研究对象,以17名健康儿童作对照。将其外周血单个核细胞(PBMC)分成两份:一份用于活化T细胞,另一份进一步分离出单核细胞并分别培养。设1α,25(OH)2D3干预组和对照组,收集培养上清液。ELISA检测上清液中干扰素(IFN)-γ、白细胞介素(IL)-4、IL-10、IL-12水平。结果HT组PB-MC产生IFN-γ、IL-12质量浓度显著高于健康对照,分别为(2146.15±355.01)pg/mL和(1462.00±101.52)pg/mL(P<0.01)、(119.18±28.65)pg/mL和(102.84±23.86)pg/mL(P<0.01);而IL-4、IL-10的表达显著低于健康对照组,分别为(52.26±7.17)pg/mL和(59.32±4.21)pg/mL(P<0.01)、(132.99±12.04)pg/mL和(171.41±35.72)pg/mL(P<0.01)。1α,25(OH)2D3干预后HT患儿IFN-γ、IL-12表达显著下调,分别为(1536.00±243.95)pg/mL(P<0.01)、(98.57±11.98)pg/mL(P<0.01);IL-10表达在HT组和健康对照组均上调,分别为(184.15±35.34)pg/mL(P<0.01)、(223.77±53.36)pg/mL(P<0.01);IL-4的变化不明显(P>0.05);IFN-γ/IL-4比值显著降低,IL-10/IL-12比值显著升高。结论在T细胞和抗原提呈细胞水平,1α,25(OH)2D3能通过抑制HT增强的TH1型细胞因子分泌,纠正TH1/TH2细胞因子失衡。理论上1α,25(OH)2D3可作为免疫调节剂改善儿童HTTH1/TH2细胞因子失衡。
Objective To investigate the effects of 1α, 25 (OH) 2D3 on the levels of TH1 / TH2 cytokines in Hashimoto’s thyroiditis (HT) in children and monocytes. The imbalance of HTTH1 / TH2 in children with 1α, 25 Provide a theoretical basis. Methods Twenty-seven cases of HT children admitted to Children’s Hospital of Chongqing Medical University from July 2003 to August 08 were enrolled in this study. Seventeen healthy children were used as controls. Peripheral blood mononuclear cells (PBMCs) were divided in two: one for T cells activation and one for further isolation of mononuclear cells and culture separately. The 1α, 25 (OH) 2D3 intervention group and control group were collected culture supernatant. The levels of IFN-γ, IL-4, IL-10 and IL-12 in the supernatant were detected by ELISA. Results The levels of IFN-γ and IL-12 produced by PB-MC in HT group were significantly higher than those in healthy controls (2146.15 ± 355.01 pg / mL and 1462.00 ± 101.52 pg / mL, respectively (52.66 ± 7.17) pg / mL and (59.32) pg / mL, respectively (P <0.01), while the levels of IL-4 and IL-10 were significantly lower than those of healthy controls ± 4.21 pg / mL (P <0.01), (132.99 ± 12.04) pg / mL and (171.41 ± 35.72) pg / mL, respectively. The levels of IFN-γ and IL-12 in HT children were significantly decreased after intervention with 1α, 25 (OH) 2D3, respectively (P <0.01) and (98.57 ± 11.98) pg / 0.01). The expression of IL-10 was up-regulated in HT group and healthy control group (184.15 ± 35.34) pg / mL (223.77 ± 53.36) pg / mL (P> 0.05). The ratio of IFN-γ / IL-4 was significantly decreased and the ratio of IL-10 / IL-12 was significantly increased. Conclusions 1α, 25 (OH) 2D3 can correct the imbalance of TH1 / TH2 cytokines by inhibiting HT-enhanced TH1-type cytokine secretion at T cell and antigen presenting cell level. Theoretically, 1α, 25 (OH) 2D3 can be used as an immunomodulator to improve HTTH1 / TH2 cytokine imbalance in children.