儿童EBV传染性单核细胞增多症细胞因子IL-6、γ-IFN、IL-10的改变

Changes of cytokines IL-6,γ-IFN,IL-10 in EBV infectious mononucleosis in children

目的探讨EB病毒(EBV)感染的传染性单核细胞增多症(IM)患儿淋巴细胞亚群和细胞因子IL-6、γ-IFN、IL-10的变化及临床意义。方法选择2018年9月至2020年8月苏州大学附属儿童医院感染科收治的EBV感染的IM患儿100例作为病例组。同期在苏州大学附属儿童医院儿童保健科体检的健康儿童60名作为对照组。采用流式细胞术和酶联免疫吸附试验分别检测IM患儿及对照组的外周血淋巴细胞亚群和细胞因子(IL-6、IL-10、γ-IFN)水平。结果病例组细胞因子IL-6、IL-10、γ-IFN高于对照组(P<0.05或0.001)。病例组CD3^(+)、CD3^(+)CD8^(+)百分比高于对照组,而CD3^(+)CD4^(+)、CD19^(+)CD23^(+)、CD3^(-)CD(16+56)+、CD3^(-)CD19^(+)百分比、CD4^(+)/CD8^(+)比值低于对照组,两组差异均有统计学意义(P<0.001)。两组间异型淋巴细胞百分比、WBC、ALT、AST、LDH差异均有统计学意义(P<0.05或0.01)。病例组IL-6与异型淋巴细胞百分比、WBC、血浆EBV-DNA病毒载量、ALT、LDH无相关性(P>0.05),与AST呈正相关(P<0.05)。病例组IL-10与异型淋巴细胞百分比、WBC、血浆EBV-DNA病毒载量、ALT、AST、LDH均无相关性(P>0.05)。病例组γ-IFN与异型淋巴细胞百分比、WBC、ALT、LDH无相关性(P>0.05),与血浆EBV-DNA病毒载量和AST呈正相关(P<0.05)。病例组IL-6与CD3^(+)、CD3^(+)CD8^(+)百分比呈负相关(P<0.05或0.001),与CD3^(+)CD4^(+)、CD3^(-)CD19^(+)百分比、CD4^(+)/CD8^(+)呈正相关(P<0.05或0.001),与CD19^(+)CD23^(+)、CD3^(-)CD(16+56)^(+)百分比无相关性(P>0.05)。病例组IL-10与CD19^(+)CD23^(+)、CD3^(-)CD19^(+)百分比呈正相关(P<0.05),与CD3^(+)呈负相关(P<0.05),与CD3^(+)CD4^(+)、CD3^(+)CD8^(+)、CD3^(-)CD(16+56)^(+)百分比、CD4^(+)/CD8^(+)无相关性(P>0.05)。病例组γ-IFN与CD3^(+)、CD3^(+)CD8^(+)百分比呈负相关(P<0.05),与CD19^(+)CD23^(+)、CD3^(+)CD4^(+)、CD3^(-)CD(16+56)^(+)、CD3^(-)CD19^(+)百分比、CD4^(+)/CD8^(+)无相关性(P>0.05)。结论EBV感染的传染性单核细胞增多症患儿的免疫改变和炎症反应与疾病的发生、发展有关,IL-6、IL-10、γ-IFN参与传染性单核细胞增多症的免疫发病过程。

Objective To investigate the changes of lymphocyte subsets,cytokines IL-6,γ-IFN and IL-10 in infectious mononucleosis(IM)children infected with Epstein-Barr virus(EBV)and their clinical significance.Methods A total of 100 children with EBV infected IM who were admitted to the Infectious Diseases Department of Children's Hospital of Soochow University from September 2018 to August 2020 were selected as case group.A total of 60 healthy children who underwent physical examination in the child health care department in the same hospital during the same period were selected as control group.The levels of lymphocyte subsets and cytokines(IL-6,IL-10,andγ-IFN)in peripheral blood of the children with IM and the control group were tested by flow cytometry and enzyme-linked immunosorbent assay,respectively.Results The cytokine levels of IL-6,IL-10,andγ-IFN in the case group were higher than those in the control group(P<0.05 or 0.001).CD3^(+)and the percentage of CD3^(+)CD8^(+)in the case group were higher than those in the control group,while the percentages of CD3^(+)CD4^(+),CD19^(+)CD23^(+),CD3^(-)CD(16+56)^(+),CD3^(-)CD19^(+),and CD4^(+)/CD8^(+)ratio were lower than those in the control group,and the differences between the two groups were statistically significant(P<0.001).There were all statistically significant differences in the percentage of atypical lymphocytes,WBC,ALT,AST,and LDH between the two groups(P<0.05 or 0.01).There was no correlation between IL-6 and the percentage of atypical lymphocytes,WBC,plasma EBV-DNA viral load,ALT,and LDH in the case group(P>0.05),but there was a positive correlation with AST(P<0.05).There was no correlation between IL-10 and the percentage of atypical lymphocytes,WBC,plasma EBV-DNA viral load,ALT,AST,and LDH in the case group(P>0.05).In the case group,γ-IFN had no correlation with the percentage of atypical lymphocytes,WBC,ALT,LDH(P>0.05),but it was positively correlated with plasma EBV-DNA viral load and AST(P<0.05).In the case group,IL-6 was negatively correlated with CD3^(+),the percentage of CD3^(+)CD8^(+)(P<0.05 or 0.001),positively correlated with the percentages of CD3^(+)CD4^(+),CD3^(-)CD19^(+)and CD4^(+)/CD8^(+)(P<0.05 or 0.001),but it was not correlated with the percentages of CD19^(+)CD23^(+),and CD3^(-)CD(16+56)^(+)(P>0.05).In the case group,IL-10 was positively associated with the percentages of CD19^(+)CD23^(+),CD3^(-)CD19^(+)percentage(P<0.05),negatively with CD3^(+)(P<0.05),and it was not correlated with the percentages of CD3^(+)CD4^(+),CD3^(+)CD8^(+),CD3^(-)CD(16+56)^(+),and CD4^(+)/CD8^(+)(P>0.05).In the case group,γ-IFN was negatively associated with CD3^(+)and the percentage of CD3^(+)CD8^(+)(P<0.05),but it had no correlation with the percentages of CD19^(+)CD23^(+),CD3^(+)CD4^(+),CD3^(-)CD(16+56)^(+),CD3^(-)CD19^(+),and CD4^(+)/CD8^(+)(P>0.05).Conclusion The immune changes and inflammatory response of EBV-infected children with IM are related to the occurrence and development of the disease,IL-6,IL-10 andγ-IFN are involved in the immunological pathogenesis of IM.