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首页> 外文期刊>Cytokine >Subcutaneous administration of recombinant glycosylated interleukin 6 in patients with cancer: pharmacokinetics, pharmacodynamics and immunomodulatory effects.
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Subcutaneous administration of recombinant glycosylated interleukin 6 in patients with cancer: pharmacokinetics, pharmacodynamics and immunomodulatory effects.

机译：在癌症患者中皮下注射重组糖基化白介素6：药代动力学，药效学和免疫调节作用。

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This is the first report of the serum profile of a glycosylated recombinant form of human IL-6 (rhIL-6) administered subcutaneously (1-10 microg/kg/day) in a phase I/II trial as a thrombopoietic agent in patients with advanced cancer. The pharmacodynamic effects of IL-6 were also examined. Detailed pharmacokinetic measurements were made in four patients. Peak concentrations at 5-8 h and a median t0.5 of ca. 5 h were similar to those previously reported for non-glycosylated IL-6. However, higher peak concentrations and apparent differences in effective dose levels to those previously reported with the non-glycosylated form were seen. Indications of an apparent attenuation in circulating IL-6 concentrations with continuing injections were seen in eight of 10 patients examined but anti-IL-6 antibody generation was seen in only two patients. Soluble interleukin 6 receptor concentrations generally decreased. No major changes in T cell subsets were seen but expression of CD25 and CD54 by T lymphocytes significantly increased, accompanied by marked increases in soluble CD25 (sIL-2R) and CD54 (sICAM-1). No consistent change in B cells, monocytes or NK cells were seen. No evidence for induction of TNF-alpha was found. This study demonstrates similar biological effects of glycosylated rhIL-6 to those reported for the non-glycosylated form but illustrates several apparent differences which are discussed further.
机译：这是在I / II期试验中作为血栓形成药物皮下注射（1-10微克/千克/天）皮下注射的人IL-6（rhIL-6）的糖基化重组形式的血清学特征的首次报道。晚期癌症。还检查了IL-6的药效学作用。在四名患者中进行了详细的药代动力学测量。在5-8小时达到峰值浓度，中位t0.5约为。 5小时类似于先前报道的非糖基化IL-6的那些。然而，与先前报道的非糖基化形式相比，可以看到更高的峰值浓度和有效剂量水平的明显差异。在接受检查的10位患者中，有8位观察到连续注射循环IL-6浓度明显降低的迹象，但只有2位患者观察到产生了抗IL-6抗体。可溶性白介素6受体浓度通常会降低。没有观察到T细胞亚群的重大变化，但是T淋巴细胞的CD25和CD54表达显着增加，同时可溶性CD25（sIL-2R）和CD54（sICAM-1）也明显增加。在B细胞，单核细胞或NK细胞中未观察到一致的变化。没有发现诱导TNF-α的证据。这项研究证明了糖基化的rhIL-6的生物学效应与非糖基化形式报道的相似，但也说明了一些明显的差异，这些差异将在以后进行讨论。

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