过敏性紫癜病儿树突细胞分泌白细胞介素-12水平与T_H1/T_H2的变化

Levels of IL-12 produced by dendritic cells and changes of TH1/TH2 balance in children with Henoch-Schonlein purpura

摘要:

目的：观察过敏性紫癜(HSP)病儿外周血树突细胞(DC)产生IL12的变化,并探讨其对TH1/TH2平衡的影响及在HSP发病机制中的意义。方法：应用酶联免疫吸附试验(ELISA)检测60例HSP病儿(HSP组)及21例健康儿童(对照组)血浆干扰素γ(IFNγ)、白细胞介素4(IL4)、白细胞介素12(IL12)水平。并对其中22例HSP病儿及21例健康儿童外周血单个核细胞(PBMC)进行体外培养以诱生出DC,用ELISA法检测培养上清液中IL12水平,同时应用间接免疫荧光法检测CD1a+细胞表达率。结果：①HSP组血浆IFNγ水平低于对照组(30.59±11.27pg/mLvs43.38±19.19pg/mL,P<0.01),IL4水平高于对照组(45.08±9.19pg/mLvs32.95±7.10pg/mL,P<0.01),IFNγ/IL4比值低于对照组(0.70±0.28vs1.33±0.57,P<0.01),IL12水平低于对照组(153.95±91.88pg/mLvs323.06±162.34pg/mL,P<0.01);HSP组和对照组各自血浆中IL12水平与IFNγ水平呈正相关(P<0.01,0.05),与IL4水平无相关性(P>0.05),与IFNγ/IL4比值呈正相关(P<0.01)。②HSP组培养上清液IL12水平低于对照组(357.06±153.56pg/mLvs489.80±213.45pg/mL,P<0.05),且与血浆IL12水平呈正相关(P<0.01)。③HSP组CD1a+细胞表达率低于对照组(27.42±10.75)%vs(35.68±12.18)%,(P<0.05),与培养上清液和血浆IL12水平皆呈正相关(P<0.01)。结论：HSP病儿存在TH1/TH2平衡失调,TH1功能的下降与血浆IL12水平低下呈正相关,而后者又与DC数量减少和/或功能低下关系密切,表明HSP病儿外周血DC数量减少和/或功能低下间接导致了TH1/TH2平衡的失调。

Abstract:

OBJECTIVE: To study the changes of IL-12 produced by dendritic cells in peripheral blood in children with Henoch-Schonlein purpura (HSP), and to explore its influence on TH1/TH2 balance in order to elucidate its significance in the pathogenesis of HSP. METHODS: The levels of interferon-γ (IFN-γ), interleukin-4 (IL-4) and interleukin-12 (IL-12) in plasma were determined by ELISA in 60 HSP children (HSP group) and 21 healthy children (Control group). Peripheral blood mononuclear cells (PBMC) of 22 HSP patients and 21 healthy children were cultured in vitro and then were transformed into dendritic cells. The levels of IL-12 in the supernatant were detected by ELISA and the positive expression rate of CD1a+ was detected by indirect immunofluorescence procedure. RESULTS: ①The levels of IFN-γ and the ratio of IFN-γ/IL-4 in plasma of the HSP group were lower than those of the Control group (IFN-γ 30.59± 11.27 pg/mL vs 43.38±19.19 pg/mL; IFN-γ/IL-4 ratio 0.70±0.28 vs 1.33±0.57) (P<0.01). The levels of IL-12 in the HSP group were also lower than those of the Control group (153.95±91.88 pg/mL vs 323.06±162.34 pg/mL; P<0.01). In contrast, the levels of IL-4 were higher than those of the Control group (45.08±9.19 pg/mL vs 32.95±7.10 pg/mL; P<0.01). The plasma levels of IL-12 positively correlated with the IFN-γ levels (r=0.52, P<0.01) and the ratio of IFN-γ/IL-4 (r=0.43, P<0.01) in the HSP group. ②The IL-12 levels in the supernatant of the HSP group were lower than those of the Control group (357.06±153.56 pg/mL vs 489.80±213.45 pg/mL; P<0.05), and had a positive correlation with the plasma IL-12 levels (r=0.74, P<0.01). ③The positive expression rate of CD1a+ of the HSP group was lower than that of the Control group [(27.42±10.75)% vs (35.68±12.18)%; P<0.05], and positively correlated with the IL-12 levels in the supernatants (r=0.57, P<0.01) and in plasma (r=0.68, P<0.01). CONCLUSIONS: There was an imbalance of TH1/TH2 in HSP children. The decrease of TH1 function had a positive correlation with the low levels of IL-12 in plasma, while the latter correlated closely with decreased number and / or function of dendritic cells, suggesting that the decreased number and / or function of dendritic cells in peripheral blood resulted in the imbalance of TH1/TH2 indirectly.