Proinflammatory effects of IL-10 during human endotoxemia

Proinflammatory effects of IL-10 during human endotoxemia
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DOI:
10.4049/jimmunol.165.5.2783
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发表时间:
2000-09-01
影响因子:
4.4
通讯作者:
van der Poll, T
van der Poll, T
中科院分区:
医学2区
文献类型:
--
作者:
Lauw, FN;Pajkrt, D;van der Poll, T

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IL-10被认为是一种有效的抗炎细胞因子,可以强烈抑制促炎细胞因子的产生。最近的研究表明,IL-10对CD4(+)、CD8(+) T细胞和/或NK细胞也具有免疫刺激特性,导致tfn - γ产生增加。为了确定IL-10对人类ifn - γ产生和相关炎症反应的影响,16名健康受试者接受了LPS (4 ng/kg)联合安慰剂或重组人IL-10 (25 mug/kg)的静脉注射,在LPS治疗前或治疗后1小时给药,特别是在LPS治疗后给药,增强了LPS诱导的ifn - γ释放。以及ifn - γ依赖性趋化因子ifn - γ诱导蛋白-10和ifn - γ诱导的单因子的释放,同时抑制或不影响ifn - γ诱导细胞因子的产生,Pn添加、IL-10处理增强了LPS注射后ctl和NK细胞的活化,表现为可溶性颗粒酶水平的增加。这些数据表明,炎症性疾病患者的高剂量IL-10治疗可能与意想不到的促炎作用相关。
IL-10 is considered a potent antiinflammatory cytokine that strongly inhibits the production of proinflammatory cytokines. Recent studies have suggested that IL-10 also has immunostimulatory properties on CD4(+), CD8(+) T cells, and/or NK cells, resulting in increased TFN-gamma production. To determine the effect of IL-10 on IFN-gamma production and related inflammatory responses in humans, 16 healthy subjects received a bolus i.v. Injection of LPS (4 ng/kg) in combination with either placebo or recombinant human IL-10 (25 mug/kg), administered just before or 1 h after LPS, IL-10 treatment, particularly when administered after LPS, enhanced LPS-induced IFN-gamma release, as well as the release of the IFN-gamma -dependent chemokines IFN-gamma -inducible protein-10 and monokine induced by IFN-gamma, while inhibiting or not influencing the production of IFN-gamma -inducing cytokines, Pn addition, IL-10 treatment enhanced activation of CTLs and NK cells after LPS injection, as reflected by increased levels of soluble granzymes, These data indicate that high-dose IL-10 treatment in patients,vith inflammatory disorders can be associated with undesired proinflammatory effects.