Interleukin-6 production in posttransplant lymphoproliferative disease.

Interleukin-6 production in posttransplant lymphoproliferative disease.
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移植后淋巴增殖性疾病中白细胞介素 6 的产生。

DOI:
10.1172/jci116523
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发表时间:
1993
期刊:
The Journal of clinical investigation
影响因子:
--
通讯作者:
McKnight,JL
McKnight,JL
中科院分区:
--
文献类型:
--
作者:
Tosato,G;Jones,K;Breinig,MK;McWilliams,HP;McKnight,JL

文献摘要

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IL-6 是一种由单核细胞、成纤维细胞和内皮细胞产生的多功能细胞因子,可在体外促进 EBV 永生化 B 细胞的生长,并使这些细胞在无胸腺小鼠中致瘤。在本研究中,发现 18 名患有移植后淋巴增殖性疾病 (PTLD) 的实体器官移植受者中有 17 名的血清/血浆 IL-6 生物活性异常升高,尽管是短暂的,平均最高水平为 196.7 U/ml。这比正常平均值 (11.3 U/ml) 增加了 16.4。相比之下,移植后病程不复杂的 10 名实体器官移植受者中,只有 3 名的血清/血浆 IL-6 生物活性异常升高(平均最大水平 41.4 U/ml,P = 0.0007)。当转移至单细胞培养物时,11个PTLD组织在培养物上清液中产生640至1.25 x 10(6) IL-6 U/ml,平均最大水平为35,025 IL-6 U/ml。细胞分离实验表明,被鉴定为非 B 细胞的贴壁细胞是 PTLD 组织体外产生 IL-6 的主要来源。淋巴细胞增殖性疾病阴性的炎症淋巴组织的对照培养物以及急性 EBV 诱导的传染性单核细胞增多症患者的 PBL 培养物始终产生 < 10 IL-6 U/ml。因此,PTLD 组织产生高水平的 IL-6,可能在 PTLD 的发病机制中发挥关键作用。
IL-6, a multifunctional cytokine produced by monocytes, fibroblasts, and endothelial cells, promotes the growth of EBV-immortalized B cells in vitro and renders these cells tumorigenic in athymic mice. In the present study, serum/plasma IL-6 bioactivity was found to be abnormally elevated, albeit transiently, in 17 of 18 solid organ transplant recipients with posttransplant 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 1.25 x 10(6) 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. Control cultures of inflammatory lymphoid tissue negative for lymphoproliferative disease as well as of PBL from patients with acute EBV-induced infectious mononucleosis consistently produced < 10 IL-6 U/ml. Thus, IL-6 is produced at high levels by PTLD tissues and may play a critical role in the pathogenesis of PTLD.