Hill G R, Krenger W, Ferrara J L
a Department of Pediatric Oncology , Dana Farber Cancer Institute, Harvard Medical School , Boston , MA 02115.
Hematology. 1997;2(6):423-34. doi: 10.1080/10245332.1997.11746365.
Giaft versus host disease (GVHD) remains the principal complication limiting the wider application of allogeneic bone marrow transplantation (BMT). Advances in basic immunology during the last decade have demonstrated how interactions between immunologically competent cells are governed by cytokines, and much recent research has focused on the roles of these mediators in the pathogenesis of acute GVHD. This article will review current evidence that dysregulated cytokine production can be considered a cascade of sequential activation of T-cells and monocytes that is responsible for many of the manifestations of acute GVHD. We suggest that cytokine dysregulation can be divided into three phases. Phase 1 is initiated by the conditioning of the host, which induces inflammatory processes in recipient tissues. Donor T-cell activation by host alloantigens and subsequent cytokine secretion in Phase 2 is facilitated by the consequences of Phase 1. The T-cell derived cytokines of Phase 2 activate distal inflammatory meditators which, together with T and NK-cell-mediated cytotoxicity, produce the systemic morbidity of GVHD-associated immunosuppression in Phase 3. Data from both experimental and clinical studies involving cytokines and their blockade in the prevention or treatment of GVHD will be reviewed.
移植物抗宿主病（GVHD）仍然是限制异基因骨髓移植（BMT）广泛应用的主要并发症。过去十年基础免疫学的进展表明，免疫活性细胞之间的相互作用是如何受细胞因子调控的，并且最近的许多研究都集中在这些介质在急性移植物抗宿主病发病机制中的作用。本文将综述当前的证据，即细胞因子产生失调可被视为T细胞和单核细胞的一系列顺序激活，这是急性移植物抗宿主病许多表现的原因。我们认为细胞因子失调可分为三个阶段。第一阶段由宿主预处理引发，这会在受体组织中诱导炎症过程。第一阶段的后果促进了第二阶段宿主同种异体抗原对供体T细胞的激活以及随后的细胞因子分泌。第二阶段T细胞衍生的细胞因子激活远端炎症介质，这些介质与T细胞和NK细胞介导的细胞毒性一起，在第三阶段产生移植物抗宿主病相关免疫抑制的全身发病率。将综述来自涉及细胞因子及其在预防或治疗移植物抗宿主病中的阻断作用的实验和临床研究的数据。
