Effect of an Extract Based on the Medicinal Mushroom Agaricus blazei Murill on Release of Cytokines, Chemokines and Leukocyte Growth Factors in Human Blood Ex Vivo and In Vivo

Effect of an Extract Based on the Medicinal Mushroom Agaricus blazei Murill on Release of Cytokines, Chemokines and Leukocyte Growth Factors in Human Blood Ex Vivo and In Vivo
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DOI:
10.1111/j.1365-3083.2008.02218.x
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发表时间:
2009-03-01
影响因子:
3.7
通讯作者:
Hetland, G.
Hetland, G.
中科院分区:
医学4区
文献类型:
--
作者:
Johnson, E.;Forland, D. T.;Hetland, G.

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一种基于药用蘑菇的免疫刺激提取物(ABM)已被证明在体外刺激单核巨噬细胞产生促炎细胞因子,并对小鼠致死性腹膜炎具有保护作用。本研究的目的是研究ABM对健康志愿者体外刺激后和口服后几天体内全血中几种细胞因子释放的影响。检测的17种信号物质为;辅助性T细胞1(Th1)细胞因子[IL-2、干扰素-γ和IL-12]、辅助性T细胞2细胞因子(IL-4、IL-5和IL-13)、多效性(IL-7、IL-17)、促炎[IL-1β、IL-6、肿瘤坏死因子(TNF)-α(主要由Th1细胞产生)]和抗炎(IL-10)细胞因子、趋化因子[IL-8、IL-8、巨噬细胞抑制蛋白(MIP)-1β和单核细胞趋化蛋白(MCP)-1]和白细胞生长因子[粒细胞集落刺激因子(G-CSF),粒细胞/巨噬细胞集落刺激因子]。用0.5-5.0%的蘑菇提取物(主要含有ABM的AndoSan(TM))体外刺激全血后,所有研究的细胞因子都有剂量依赖性的增加,从2倍到399倍(肿瘤坏死因子-α)不等。然而,在体内,在8名志愿者中,每天摄入这种ABM提取物(60毫升)12天后,IL-1β(97%)、肿瘤坏死因子-α(84%)、IL-17(50%)和IL-2(46%)水平显著降低。虽然不显著,但IL-8、干扰素-伽马和粒细胞集落刺激因子水平有下降的趋势,而其余9种细胞因子的水平没有变化。体内外对细胞因子释放的不同结果可能部分是由于ABM在体内的抗氧化活性以及其大的、复杂的、具有生物活性的β-葡聚糖通过肠粘膜对网状内皮系统和血液的吸收有限所致。
An immunostimulatory extract based on the medicinal mushroom Agaricus blazei Murill (AbM) has been shown to stimulate mononuclear phagocytes in vitro to produce pro-inflammatory cytokines, and to protect against lethal peritonitis in mice. The present aim was to study the effect of AbM on release of several cytokines in human whole blood both after stimulation ex vivo and in vivo after oral intake over several days in healthy volunteers. The 17 signal substances examined were; T helper 1 (Th1) cytokines [interleukin (IL)-2, interferon (IFN)-gamma and IL-12], T helper 2 cytokines (IL-4, IL-5 and IL-13), pleiotropic (IL-7, IL-17), pro-inflammatory [IL-1 beta, IL-6, tumour necrosis factor (TNF)-alpha (mainly produced by Th1 cells)] - and anti-inflammatory (IL-10) cytokines, chemokines [IL-8, macrophage inhibitory protein (MIP)-1 beta and monocyte chemoattractant protein (MCP)-1] and leukocyte growth factors [granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony stimulating factor]. After stimulation of whole blood ex vivo with 0.5-5.0% of a mushroom extract, AndoSan (TM) mainly containing AbM, there was a dose-dependent increase in all the cytokines studied, ranging from two to 399-fold (TNF-alpha). However, in vivo in the eight volunteers who completed the daily intake (60 ml) of this AbM extract for 12 days, a significant reduction was observed in levels of IL-1 beta (97%), TNF-alpha (84%), IL-17 (50%) and IL-2 (46%). Although not significant, there was a trend towards reduced levels for IL-8, IFN-gamma and G-CSF, whilst those of the remaining nine cytokines tested, were unaltered. The discrepant results on cytokine release ex vivo and in vivo may partly be explained by the antioxidant activity of AbM in vivo and limited absorption of its large, complex and bioactive beta-glucans across the intestinal mucosa to the reticuloendothelial system and blood.