A ROLE FOR INTERLEUKIN-6 IN POST-TRANSPLANT LYMPHOPROLIFERATIVE DISEASE

EB病毒（EBV）是嗜异性阳性的病原体 急性传染性单核细胞增多症，是一种成功的病原体在人类 种，无症状地感染大多数正常成年个体。 在 尽管B细胞具有无限生长的潜力， EBV感染很少引起人类淋巴组织增生性疾病。 这种成功的抑制作用主要归功于T细胞 免疫力 严重的T细胞免疫缺陷，如发生在艾滋病 和实体器官移植受者，可能会导致不受控制的 自然感染EBV的B淋巴细胞的扩增， 淋巴增生性疾病的发展。 高达32%的固体 器官移植受者可能会患上淋巴组织增生性疾病 通常涉及EBV感染的B细胞。 IL-6，多功能 由单核细胞、成纤维细胞、内皮细胞和其他细胞产生的细胞因子 细胞类型促进EBV感染的B细胞的生长，作为一种免疫调节剂， 自分泌和/或旁分泌生长因子。 此外，这种细胞因子具有 已显示在肿瘤细胞中增加EBV永生化B细胞的致瘤性。 无胸腺小鼠 此外，血清/血浆IL-6生物活性被发现， 18个实体器官中有17个异常升高，尽管是一过性的 移植受者，移植后淋巴增生性疾病 （PTLD），平均最大水平为196.7 U/ml。 这是16.4 增加至高于正常平均值（11.3 U/ml）。 相比之下，10人中只有3人 病程简单的实体器官移植受者 移植后血清/血浆IL-6活性异常升高 (mean最高血药浓度41.4U/ml，P = 0.0007。 转单时 在细胞培养中，11个PTLD组织产生640至1.25 × 106 U/ml的IL-6。 培养上清中IL-6的平均最高水平为35，025 U/ml。 细胞分离实验表明，粘附细胞， 被鉴定为非B细胞，是IL-6产生的主要来源 在体外通过PTLD组织。 最近，我们试图识别这些细胞 负责PTLD组织中高水平的IL-6产生。 我们 初步实验表明，内皮细胞是 IL-6的细胞来源。 我们检查了几种可能的机制 诱导内皮细胞产生IL-6。 正在进行的实验 表明EBV感染内皮细胞是可能的原因 用于内皮细胞产生IL-6。 因此，IL-6在 发展PTLD和EBV的移植后接受者的循环- 淋巴组织增生性病变中受感染的内皮细胞是 可能是IL-6的来源。

Epstein-Barr virus (EBV) the causative agent of heterophile-positive acute infectious monocleosis, is a successful pathogen in the human species, asymptomatically infecting most normal adult individuals. In spite of their potential for unlimited growth, B cells naturally infected with EBV only rarely give rise to lymphoproliferative disease in man. Credit for such successful restraint is attributable, primarily to T cell immunity. Severe T cell immunodeficiency, such as that occurring in AIDS and solid organ transplant recipients, can result in the uncontrolled expansion of B lymphocytes naturally infected with EBV and the development of lymphoproliferative disease. As many as 32% of solid organ transplant recipients may develop lymphoproliferative disease generally involving EBV-infected B cells. IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, endothelial cells, and other cell types promotes growth of EBV-infected B cells, acting as an autocrine and/or paracrine growth factor. In addition, this cytokine has been shown to increase the tumorigenicity of EBV-immortalized B cells in athymic mice. Also, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 of 18 solid organ transplant recipients, with post-transplant lymphoproliferative disease (PTLD), with a mean maximal level of 196.7 U/ml. This represents a 16.4 increase above the normal mean (11.3 U/ml). In contrast, only 3 of 10 solid organ transplant recipients with uncomplicated courses posttransplant had abnormally elevated serum/plasma IL-6 bioactivity (mean maximal level 41.4 U/ml, P = 0.0007). When transferred to single cell culture, the 11 PTLD tissues produced 640 to 1.25106 IL-6 U/ml in the culture supernatant, with a mean maximal level of 35,025 IL-6 U/ml. Cell separation experiments demonstrated that the adherent cells, identified as non-B cells, were the principal source of IL-6 production in vitro by PTLD tissue. Recently, we sought to identify the cells responsible for high-level IL-6 production in PTLD tissues. Our preliminary experiments demonstrated that the endothelial cells are the cellular source of IL-6. We examined several mechanims as possibly inducing IL-6 production by endothelial cells. Ongoing experiments have indicated that EBV infection of endothelial cells is the likely reason for endothelial cell production of IL-6. Thus, IL-6 is elevated in the circulation of post transplant recipients who develop PTLD and the EBV- infected endothelial cells within the lymphoproliferative lesions are the likely source of IL-6.