肝移植后移植物抗宿主病细胞因子表达的意义

Cytokine expression during graft versus host disease after orthotopic liver transplantation

背景:预防原位肝移植术后并发症已成为目前研究热点,已有文献报道了有关细胞因子方面的研究,但是对移植物抗宿主病细胞因子检测的报道少见。目的:探索原位肝移植患者发生移植物抗宿主病后血浆细胞因子的表达及意义。设计、时间及地点:观察性实验,于2002-05/2006-09在武警总医院进行。对象:原位肝移植后确诊为移植物抗宿主病患者4例。方法:应用生物芯片技术和EVIDENCE180全自动芯片分析仪检测了4例患者在原位肝移植术后、发生移植物抗宿主病初期、中期、后期、恢复期或死亡时血清白细胞介素1α、白细胞介素1β、白细胞介素2、白细胞介素4、白细胞介素6、白细胞介素8、白细胞介素10、血管内皮生长因子、γ-干扰素、单核细胞趋化蛋白、肿瘤坏死因子α、表皮生长因子水平。主要观察指标:12种细胞因子的表达。结果:12种血浆细胞因子在移植物抗宿主病病程中表达明显不同,白细胞介素1α、白细胞介素1β、白细胞介素2、白细胞介素4在移植物抗宿主病病程中低表达或零表达,白细胞介素10除例4在移植物抗宿主病发病前高表达外,其他患者均减低,单核细胞趋化蛋白、血管内皮生长因子、白细胞介素6、表皮生长因子、白细胞介素8逐渐增高或持续高表达,γ-干扰素仅在移植物抗宿主病发病初期轻微增高,肿瘤坏死因子α随病程轻微增高。结论:原位肝移植后发生移植物抗宿主病病程中,单核细胞趋化蛋白、血管内皮生长因子、白细胞介素6、表皮生长因子、白细胞介素8、白细胞介素10细胞因子在免疫相关损伤中起了重要作用,白细胞介素1、白细胞介素2、白细胞介素4低表达也是重要特征。

BACKGROUND： Prevention of the common complication after orthotopic liver transplantation is a hot topic, and there are studies on cytokines. But reports on the graft versus host disease （GVHD） cytokines are not available. OBJECTIVE： To study the expression and significance of plasma cytokines in GVHD after orthotopic liver transplantation. DESIGN, TIME AND SETTING： The observational experiment was performed at the General hospital of Chinese People＇s Armed Police Forces from May 2002 to September 2006. PARTICIPANTS： Four patients, who had been diagnosed as having GVHD after orthotopic liver transplantation, were recruited. METHODS： Biochip technology and EVIDENCE 180 full automatic biochip analyzer were used to evaluate the levels of interleukin （IL） 1α, IL 1β, IL 2 , IL 4 , IL 6 , IL 8, IL 10, vascular endothelial growth factor （VEGF）, interferon （IFN） γ, monocyte chemoattractant protein （MCP）, tumor necrosis factor a and epidermal growth factor （EGF） of 4 patients after orthotopic liver transplantation and initial, mediate, later, recover/death phases of GVHD. MAIN OUTCOME MEASURES： Twelve forms of cytokine expression. RESULTS： Expression of 12 cytokines was different. The IL-1α, IL-1 β, IL-2, IL-4 levels were maintained low value or zero during the whole study period. IL-10 decreased apart from case 4, which reached maximum level before GVHD. MCP-1, VEGF, IL-6, EGF, IL-8 increased progressively or maintaining high concentrations during GVHD. IFN- γ only slightly increased in initial stage of GVHD. A slight increase in TNF- α was detected. CONCLUSION： MCP-1, VEGF, IL-6, EGF, IL-8, IL-10 play an important role in linking injury during GVHD after orthotopic liver transplantation. Low expression of IL 1, IL2 and IL4 is a crucial feature.