巨细胞病毒肝炎婴儿外周血IL-33、sST2表达及意义
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摘要
目的探讨白细胞介素-33(IL-33)、可溶性致癌抑制因子2(sST2)在婴儿巨细胞病毒(HCMV)肝炎中的表达及意义。方法选取HCMV感染婴儿40例,其中肝炎组20例,其他疾病组20例;另选择同期健康婴儿20例作为对照组。采用ELISA法检测三组婴儿血浆IL-33、sST2、IFN-γ、IL-4浓度,采用流式细胞术检测外周血Th1、Th2细胞比例。结果HCMV阳性肝炎组和HCMV阳性其他疾病组患儿的血浆IL-33、sST 2、IFN-γ、IL-4浓度及Th 1、Th 2细胞比例均高于对照组,肝炎组高于其他疾病组。肝炎组和其他疾病组患儿IFN-γ/IL-4及Th1/Th2均低于对照组,肝炎组低于其他疾病组,差异均有统计学意义(P<0.05)。HCMV肝炎组血浆IL-33浓度与sST2、IL-4浓度及Th2细胞比例呈显著正相关(P<0.05),与IFN-γ/IL-4、Th1/Th2呈显著负相关(P<0.05)。结论 HCMV肝炎婴儿存在Th1/Th2失衡,IL-33可能参与HCMV感染所致Th2优势应答和Th1/Th2失衡。
Objective To explore the expression and significance of interleukin-33(IL-33) and soluble suppression of tumorigenicity 2(sST 2) in human cytomegalovirus(HCMV) hepatitis in infants. Methods Forty infants with HCMV infection were selected, including 20 in hepatitis group and 20 in other diseases group, and 20 healthy infants in the same period were selected as the control group. The plasma levels of IL-33, sST2, IFN-γ and IL-4 were measured by ELISA,and the ratio of Th1 and Th2 cells in peripheral blood was measured by flow cytometry. Results The plasma levels of IL-33, sST2, IFN-γ, IL-4 and the proportion of Th1 and Th2 cells in HCMV-positive hepatitis group and other diseases group were higher than those in the control group, and they were higher in hepatitis group than in other diseases group. The levels of IFN-γ/IL-4 and Th1/Th2 in hepatitis group and other diseases group were lower than those in the control group, and they were lower in hepatitis group than in other diseases group. The differences were statistically significant(P<0.05). Plasma IL-33 concentration in HCMV-positive hepatitis group was positively correlated with sST 2 and IL-4 concentrations and the proportion of Th 2 cell(P<0.05), while it was negatively correlated with the IFN-γ/IL-4 and Th1/Th2(P< 0. 05). Conclusion Th 1/Th 2 imbalance exists in infants with HCMV hepatitis. IL-33 may be involved in Th 2 dominant response and Th 1/Th 2 imbalance caused by HCMV infection.
Objective To explore the expression and significance of interleukin-33(IL-33) and soluble suppression of tumorigenicity 2(sST 2) in human cytomegalovirus(HCMV) hepatitis in infants. Methods Forty infants with HCMV infection were selected, including 20 in hepatitis group and 20 in other diseases group, and 20 healthy infants in the same period were selected as the control group. The plasma levels of IL-33, sST2, IFN-γ and IL-4 were measured by ELISA,and the ratio of Th1 and Th2 cells in peripheral blood was measured by flow cytometry. Results The plasma levels of IL-33, sST2, IFN-γ, IL-4 and the proportion of Th1 and Th2 cells in HCMV-positive hepatitis group and other diseases group were higher than those in the control group, and they were higher in hepatitis group than in other diseases group. The levels of IFN-γ/IL-4 and Th1/Th2 in hepatitis group and other diseases group were lower than those in the control group, and they were lower in hepatitis group than in other diseases group. The differences were statistically significant(P<0.05). Plasma IL-33 concentration in HCMV-positive hepatitis group was positively correlated with sST 2 and IL-4 concentrations and the proportion of Th 2 cell(P<0.05), while it was negatively correlated with the IFN-γ/IL-4 and Th1/Th2(P< 0. 05). Conclusion Th 1/Th 2 imbalance exists in infants with HCMV hepatitis. IL-33 may be involved in Th 2 dominant response and Th 1/Th 2 imbalance caused by HCMV infection.
引文
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[12]董永绥.婴儿巨细胞病毒性肝炎(上)[J].临床儿科杂志,2006,24(1):74-77.
[13]Bilgic I,Gelecek S,Akgun AE,et al.Predictive value of liver transaminases levels in abdominal trauma[J].Am J Emerg Med,2014,32(7):705-708.
[14]Marvie P,Lisbonne M,L'helgoualc'h A,et al.Interleukin-33overexpression is associated with liver fibrosis in mice and humans[J].J Cell Mol Med,2010,14(6B):1726-1739.
[15]Xu D,Chan WL,Leung BP,et al.Selective expression of a stable cell surface molecule on type 2 but not type 1 helper Tcells[J].J Exp Med,1998,187(5):787-794.
[16]Schmitz J,Owyang A,Oldham E,et al.IL-33,an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines[J].Immunity,2005,23(5):479-490.
[17]Tago K,Noda T,Hayakawa M,et al.Tissue distribution and subcellular localization of a variant form of the human ST2gene product,ST2V[J].Biochem Biophys Res Commun,2001,285(5):1377-1383.
[18]Liew FY,Pitman NI,McInnes IB.Disease-associated functions of IL-33:the new kid in the IL-1 family[J].Nat Rev Immunol,2010,10(2):103-110.
[19]侯建明,吴贺文.HBeA阳性慢性乙型肝炎患者肝功能损伤程度与细胞因子水平的相关性研究[J].肝脏,2017,22(5):429-431.
[20]邱佩佩,李小英.原因不明复发性流产患者Th1/Th2型细胞因子的表达分析[J].中国妇幼保健,2015,30(9):1414-1416.
[21]熊菀,刘瑜,陈琼,等.细胞因子水平改变在婴儿巨细胞病毒感染中的临床意义[J].第三军医大学学报,2007,29(7):623-625.
[2]Landolfo S,Gariglio M,Gribaudo G,et al.The human cytomegalovirus[J].Pharmacol Ther,2003,98(3):269-297.
[3]方峰.巨细胞病毒感染与肝脏损害[J].实用儿科临床杂志,2006,21(10):582-583.
[4]刘玲玲,黄媛,马迪,等.参与巨细胞病毒肝炎致病机制的研究[J].中国免疫学杂志,2018,34(1):31-35.
[5]Chen WY,Tsai TH,Yang JL,et al.Therapeutic strategies for targeting IL-33/ST2 signalling for the treatment of inflammatory diseases[J].Cell Physiol Biochem,2018,49(1):349-358.
[6]Cayrol C,Girard JP.Interleukin-33(IL-33):a nuclear cytokine from the IL-1 family[J].Immunol Rev,2018,281(1):154-168.
[7]Arshad MI,Khan HA,Noel G,et al.Potential therapeutic aspects of alarmin cytokine interleukin 33 or its inhibitors in various diseases[J].Clin Ther,2016,38(5):1000-1016.
[8]中华医学会儿科学分会感染学组,全国儿科临床病毒感染协作组,中华儿科杂志编辑委员会,等.儿童巨细胞病毒性疾病诊断和防治的建议[J].中华儿科杂志,2012,50(4):290-292.
[9]中华医学会肝病学分会药物性肝病学组.药物性肝损伤诊治指南[J].肝脏,2015,20(10):750-762.
[10]曾庆贺,董加秀,孟艳,等.人巨细胞病毒感染的流行病学研究进展[J].山东医药,2017,57(12):110-116.
[11]肖咏梅,胡志红.不同年龄阶段儿童巨细胞病毒感染的临床表现差异[J].中国当代儿科杂志,2010,12(1):21-23.
[12]董永绥.婴儿巨细胞病毒性肝炎(上)[J].临床儿科杂志,2006,24(1):74-77.
[13]Bilgic I,Gelecek S,Akgun AE,et al.Predictive value of liver transaminases levels in abdominal trauma[J].Am J Emerg Med,2014,32(7):705-708.
[14]Marvie P,Lisbonne M,L'helgoualc'h A,et al.Interleukin-33overexpression is associated with liver fibrosis in mice and humans[J].J Cell Mol Med,2010,14(6B):1726-1739.
[15]Xu D,Chan WL,Leung BP,et al.Selective expression of a stable cell surface molecule on type 2 but not type 1 helper Tcells[J].J Exp Med,1998,187(5):787-794.
[16]Schmitz J,Owyang A,Oldham E,et al.IL-33,an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines[J].Immunity,2005,23(5):479-490.
[17]Tago K,Noda T,Hayakawa M,et al.Tissue distribution and subcellular localization of a variant form of the human ST2gene product,ST2V[J].Biochem Biophys Res Commun,2001,285(5):1377-1383.
[18]Liew FY,Pitman NI,McInnes IB.Disease-associated functions of IL-33:the new kid in the IL-1 family[J].Nat Rev Immunol,2010,10(2):103-110.
[19]侯建明,吴贺文.HBeA阳性慢性乙型肝炎患者肝功能损伤程度与细胞因子水平的相关性研究[J].肝脏,2017,22(5):429-431.
[20]邱佩佩,李小英.原因不明复发性流产患者Th1/Th2型细胞因子的表达分析[J].中国妇幼保健,2015,30(9):1414-1416.
[21]熊菀,刘瑜,陈琼,等.细胞因子水平改变在婴儿巨细胞病毒感染中的临床意义[J].第三军医大学学报,2007,29(7):623-625.