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

INTERLEUKIN-6 在移植后淋巴细胞增殖性疾病中的作用

• 批准号: 3748223
• 负责人: G TOSATO
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3748223
• 关键词: Epstein Barr virus; athymic mouse; autocrine; cytokine; fibroblasts; growth factor; human tissue; immunodeficiency; interleukin 6; monocyte; paracrine; postoperative complications; vascular endothelium

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.

eb病毒（EBV）是嗜异性恋阳性的病原体