A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses.
A randomized, controlled trial of IL-10 in humans. Inhibition of inflammatory cytokine production and immune responses.
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DOI：
10.4049/jimmunol.154.10.5492
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发表时间：
1995-05
影响因子：
4.4
通讯作者：
A. Chernoff;E. Granowitz;L. Shapiro;E. Vannier;G. Lonnemann;J. Angel;J. Kennedy;A. Rabson;S. Wolff;C. Dinarello
中科院分区：
文献类型：
--
作者：
A. Chernoff;E. Granowitz;L. Shapiro;E. Vannier;G. Lonnemann;J. Angel;J. Kennedy;A. Rabson;S. Wolff;C. Dinarello
在体外，IL-10抑制T细胞增殖和LPS诱导的单核细胞产生IL-1、TNF-α、IL-6和IL-8。我们研究了IL-10给药在人体中的安全性和免疫调节作用。17名健康志愿者接受了单次静脉推注人IL-10（1、10或25微克/公斤）或安慰剂。在注射前和注射后3、6、24和48 h评估常规安全性参数、淋巴细胞表型、T细胞增殖反应和刺激诱导的细胞因子产生。IL-10给药后无不良症状或体征。观察到一过性嗜中性粒细胞增多和单核细胞增多，在6 h达到峰值（高于基线45-160%）。而淋巴细胞计数在注射后3和6 h下降了25%（p < 0.01）。特别是，表达T细胞表面标志物CD 2、CD 3、CD 4、CD 7和CD 8的淋巴细胞显著减少。在两个较高剂量组中，丝裂原诱导的T细胞增殖被抑制高达50%（p < 0.01）。在每次剂量的IL-10后，从用内毒素离体刺激的全血产生的TNF-α和IL-1 β的显著剂量依赖性抑制（65-95%）发生。相反，它们各自的拮抗剂，TNF可溶性受体p55或IL-1受体拮抗剂的产生没有减少。我们得出结论，单次静脉注射IL-10对人体是安全的，对T细胞具有抑制作用，并抑制促炎细胞因子TNF-α和IL-1 β的产生。
In vitro, IL-10 inhibits T cell proliferation and LPS-induced monocyte production of IL-1, TNF-alpha, IL-6, and IL-8. We studied the safety and immunomodulatory effects of IL-10 administration in humans. Seventeen healthy volunteers received a single i.v. bolus injection of either human IL-10 (1, 10, or 25 micrograms/kg) or placebo. Routine safety parameters, lymphocyte phenotypes, T cell proliferative responses, and stimulus-induced cytokine production were assessed before and 3, 6, 24, and 48 h after injection. There were no adverse symptoms or signs after IL-10 administration. A transient neutrophilia and monocytosis that peaked at 6 h (45-160% above base line) was observed. However, lymphocyte counts fell by 25% 3 and 6 h after the injection (p < 0.01). In particular, lymphocytes expressing the T cell surface markers CD2, CD3, CD4, CD7, and CD8 were significantly decreased. Mitogen-induced T cell proliferation was suppressed by up to 50% (p < 0.01) in the two higher dose groups. Significant dose-dependent inhibition (65-95%) of TNF-alpha and IL-1 beta production from whole blood stimulated ex vivo with endotoxin occurred after each dose of IL-10. In contrast, there was no reduction in the production of their respective antagonists, TNF soluble receptor p55 or IL-1 receptor antagonist. We conclude that a single intravenous injection of IL-10 is safe in humans, has inhibitory effects on T cells, and suppresses production of the pro-inflammatory cytokines TNF-alpha and IL-1 beta.