Influence of interferon β-1a dose frequency on PBMC cytokine secretion and biological effect markers
Influence of interferon β-1a dose frequency on PBMC cytokine secretion and biological effect markers
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DOI：
10.1016/s0165-5728(99)00029-6
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发表时间：
1999-09-01
影响因子：
3.3
通讯作者：
Biollaz, J
中科院分区：
文献类型：
--
作者：
Rothuizen, LE;Buclin, T;Biollaz, J
干扰素- β方案治疗免疫介导的疾病，如多发性硬化症（MS），尚未对其生物学效应进行比较。在这项随机、平行组、安慰剂对照的研究中，研究人员评估了接受皮下重组IFN β -la (Rebif(R), Ares-Serono) 22 μ g每周一次（QW）， 22 μ g每周一次（QW）， 66 μ g QW或安慰剂治疗的志愿者中，有丝分裂原刺激的PBMCs分泌细胞因子和血清反应标志物。每次注射后24-48小时内，IL-1 β、IL-6、ifn - γ、tnf - α和tnf - α的产生明显下降，剂量依赖性有限，1个月后无耐受性或效果增强的证据。IL-IO分泌维持不变。血清β(2)（_）微球蛋白、新蝶呤和2- 5a合成酶的升高更为持续。因此，ifn - β诱导的体内免疫调节在很大程度上取决于给药计划，当相同的周剂量分为三次注射时，时间整合效应会增加2-3倍。(C)1999 Elsevier Science B.V.版权所有
Interferon-beta regimens for immune-mediated diseases, such as multiple sclerosis (MS), have not been compared regarding their biological effects. In this randomized, parallel-group, placebo-controlled study, cytokine secretion by mitogen-stimulated PBMCs and serum response markers were assessed in volunteers receiving subcutaneous recombinant IFN beta-la (Rebif(R), Ares-Serono) 22 mu g once a week (QW), 22 mu g three times a week, 66 mu g QW, or placebo. The production of IL-1 beta, IL-6, IFN-gamma, TNF-alpha and TNF-alpha markedly decreased during 24-48 h after each injection, with limited dose-dependency and no evidence of tolerance or effect augmentation over 1 month. IL-IO secretion remained unchanged. The increase in serum beta(2)(_)microglobulin, neopterin and 2-5A-synthetase was more sustained. Thus, IFN-beta-induced immunomodulation in vivo strongly depends on the administration schedule, the time-integrated effect being 2-3 times greater when a same weekly dose is divided is in three injections. (C)1999 Elsevier Science B.V. All rights reserved.