IL-18BP对急性移植物抗宿主病的影响及机制研究

Effect and mechanism of IL-18BP on acute graft-versus-host disease

目的:探讨白细胞介素18结合蛋白(IL-18BP)对小鼠异基因骨髓移植后急性移植物抗宿主病(aGVHD)的影响及作用机制。方法:C57BL/6小鼠随机分为A、B 2组,经致死量60Coγ射线照射后,经尾静脉移植入BALB/c小鼠骨髓细胞和脾脏细胞。移植后,A组注射NS;B组注射IL-18BP。比较A、B 2组小鼠aGVHD的程度,酶联免疫法(ELISA)测定血清中Th1类细胞因子干扰素-γ(IFN-γ)、白细胞介素2(IL-2)及Th2类细胞因子白细胞介素10(IL-10)、白细胞介素4(IL-4)的浓度。结果:移植后,B组小鼠较A组小鼠的aGVHD程度轻,血清IFNγ-、IL-2的浓度低,血清IL-10、IL-4的浓度高。结论:①IL-18BP可以减轻异基因骨髓移植后aGVHD反应;②IL-18BP促进Th1/Th2平衡向Th2漂移,可能是IL-18BP减轻aGVHD反应的机制之一。

Objective：To investigate the effect and the mechanism of intedeukin-18 binding protein（IL-18BP） on acute graftversus-host disease（aGVHD） in allogeneie bone marrow transplantation（ allo-BMT ） in mice. Methods：C57BL/6 recipient mice irradiated with ^60Co were randomly divided into 2 groups： group A and B and were transfused with BALB/c donor cells. After transplantation recipient mice in group A were treated with NS subcutaneously daily from day 0 to day 5 and recipient mice in group B with 1μg IL-18BP,separately. The severity of aGVHD was evaluated in the two groups. Concentrations of IFN-γ, IL-2, IL-4 and IL-10 were measured using enzyme-linked immunosorbent assay（ELISA）. Results：aGVHD response was more severe in group A than that in group B. The serum concentrations of IFN-γ and IL-2 in group A were higher than that in group B ,while the serum concentrations of IL-10 and IL-4 were lower than that in group B. Conclusion：①IL-18BP can deerese aGVHD response;②That IL-18BP can promote the differentiation of CD4^＋T cells into CD4^＋Th2 cells ,that is promoted by IL-18BP might be one of the mechanisms of decreasing aGVHD.