Ju X P, Xu B, Xiao Z P, Li J Y, Chen L, Lu S Q, Huang Z X
Department of Radiotherapy, Changhai Hospital, Shanghai, China.
Bone Marrow Transplant. 2005 Jun;35(12):1179-86. doi: 10.1038/sj.bmt.1704972.
Acute graft-versus-host disease (aGVHD) is one of the major problems following allogeneic peripheral blood stem cell transplantation (allo-PBSCT). In order to investigate the pathogenesis of human aGVHD, we analyzed cytokine gene expression and cytokine secretion by peripheral blood mononuclear cells (PBMC) in 30 patients who underwent allo-PBSCT. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to explore the mRNA expression of interleukin (IL)-2, interferon (IFN)-gamma, IL-4, IL-10 and IL-12 in the PBMC of allo-PBSCT patients with aGVHD and in controls. The concentrations of these cytokines and of IL-18 were also measured by means of ELISA in medium obtained from cultured leukocytes after stimulation with PHA or LPS. Compared with the normal allo-PBSCT group (n=14), IL-2 and IFN-gamma were detected more frequently in aGVHD group (n=16). IL-12 and IL-18 were elevated, while IL-10 level decreased in the same group. There is no difference in IL-4 gene expression between patients with or without aGVHD, but the concentration of IL-4 for patients with grade II-IV aGVHD decreased. These data suggest that IL-2, IFN-gamma, IL-12 and IL-18 play important roles in the development of aGVHD in humans.
急性移植物抗宿主病(aGVHD)是异基因外周血干细胞移植(allo-PBSCT)后的主要问题之一。为了研究人类aGVHD的发病机制,我们分析了30例接受allo-PBSCT患者外周血单个核细胞(PBMC)的细胞因子基因表达和细胞因子分泌情况。在本研究中,采用逆转录-聚合酶链反应(RT-PCR)检测aGVHD的allo-PBSCT患者及对照组PBMC中白细胞介素(IL)-2、干扰素(IFN)-γ、IL-4、IL-10和IL-12的mRNA表达。还用ELISA法检测了用PHA或LPS刺激培养的白细胞后培养基中这些细胞因子及IL-18的浓度。与正常allo-PBSCT组(n = 14)相比,aGVHD组(n = 16)中IL-2和IFN-γ的检测频率更高。同一组中IL-12和IL-18升高,而IL-10水平降低。有无aGVHD的患者之间IL-4基因表达无差异,但II-IV级aGVHD患者的IL-4浓度降低。这些数据表明,IL-2、IFN-γ、IL-12和IL-18在人类aGVHD的发生发展中起重要作用。