IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans.
IL-6/IFN-beta-2 as a circulating hormone. Induction by cytokine administration in humans.
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DOI：
10.4049/jimmunol.142.5.1542
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发表时间：
1989-03
影响因子：
4.4
通讯作者：
D M Jablons;J. Mulé;J. McIntosh;P. Sehgal;L. May;C. M. Huang;S. A. Rosenberg;Michael T. Lotze
中科院分区：
文献类型：
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作者：
D M Jablons;J. Mulé;J. McIntosh;P. Sehgal;L. May;C. M. Huang;S. A. Rosenberg;Michael T. Lotze
IL-6/IFN-β 2是一个磷酸糖蛋白家族，其大小范围为19至30 kDa，其引起广泛的生理和免疫应答。已显示包括TNF在内的几种细胞因子刺激细胞培养物中的IL-6产生。在这份报告中，我们描述了快速诱导循环的生物活性IL-6的系统管理的rTNF癌症患者。低水平的IL-6活性可以检测到患者的血清中，早在5分钟后，rTNF输液。IL-6水平在rTNF推注给药后约2至3 h达到峰值，大多数病例在8 h内检测不到。IL-6在两个独立的生物测定-杂交瘤B 9增殖和肝细胞刺激因子测定中检测到。在肝细胞刺激因子测定中，IL-6的最大可检测水平范围为160至310杂交瘤生长因子单位和11-82 ng/ml。IL-6诱导减少后，系列，每日剂量的rTNF。还测定了接受IL-2或IFN-α的患者的系列血清样品的IL-6产生。接受IL-2治疗但未接受IFN-alpha治疗的患者产生低水平的IL-6（范围低于20至95个杂交瘤生长因子单位/ml）。有趣的是，在用IL-2治疗的患者中，血清TNF水平是可检测的，并且TNF活性峰值先于可测量的IL-6水平。急性期血浆蛋白和皮质类固醇的血清水平上升响应rTNF管理。C-反应蛋白增加（2.5至4.0倍）8小时内的rTNF管理和皮质醇水平上升（10至20倍）后4小时内注射rTNF。我们的结论是，rTNF管理在人导致循环IL-6的诱导，由于其广泛的活动范围，可能是一个重要的生理信号调节免疫反应。
IL-6/IFN-beta 2 is a family of phosphoglycoproteins ranging in size from 19 to 30 kDa which elicits a broad range of physiologic and immune responses. Several cytokines, including TNF, have been shown to stimulate IL-6 production in cell culture. In this report, we describe the rapid induction of circulating biologically active IL-6 by the systemic administration of rTNF to patients with cancer. Low levels of IL-6 activity could be detected in the sera of patients as early as 5 min after rTNF infusion. IL-6 levels peaked approximately 2 to 3 h after rTNF bolus administration and were undetectable in most cases within 8 h. IL-6 was detected in two separate bioassays--the hybridoma B9 proliferation and the hepatocyte-stimulating factor assay. Maximum detectable levels of IL-6 ranged from 160 to 310 hybridoma growth factor units and 11-82 ng/ml in the hepatocyte-stimulating factor assay. IL-6 induction decreased after serial, daily doses of rTNF. Serial serum samples of patients receiving IL-2 or IFN-alpha were also assayed for IL-6 production. IL-2-treated but not IFN-alpha-treated patients generated low levels of IL-6 (range less than 20 to 95 hybridoma growth factor units/ml). Interestingly, in patients treated with IL-2, serum levels of TNF were detectable and peak TNF activity preceded measurable IL-6 levels. Serum levels of acute phase plasma proteins and of corticosteroid rose in response to rTNF administration. C-reactive protein increased (2.5 to 4.0-fold) within 8 h of rTNF administration and cortisol levels rose (10- to 20-fold) within 4 h after rTNF injection. We conclude that rTNF administration in man leads to the induction of circulating IL-6 which, due to its broad range of activities, may be an important physiologic signal regulating the immune response.