IL-6 down-modulates the cytokine-enhanced antileishmanial activity in human macrophages.
IL-6 down-modulates the cytokine-enhanced antileishmanial activity in human macrophages.
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DOI：
10.4049/jimmunol.151.7.3682
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发表时间：
1993-10
影响因子：
4.4
通讯作者：
D. E. Hatzigeorgiou;S. He;J. Sobel;K. Grabstein;A. Hafner;J. Ho
中科院分区：
文献类型：
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作者：
D. E. Hatzigeorgiou;S. He;J. Sobel;K. Grabstein;A. Hafner;J. Ho
IL-6是一种由T细胞和巨噬细胞合成的细胞因子。它对不同类型的细胞具有多效性，并因其“促炎”特性而被公认。在小鼠中，IL-4、IL-5、IL-6和IL-10是由Th-2细胞产生的。由于IL-10能抑制Th-1克隆，而IL-4能广泛地使M - phi失活，因此我们在体外研究重组人IL-6对人M - phi细胞因子激活的影响。IL-6预处理诱导了剂量依赖性和时间依赖性的ifn - γ (1000 U/mL)和tnf - α (25 ng/mL)对M phi的杀伤作用。当剂量大于0.1 ~ 100 ng/mL时，IL-6对ifn - γ和tnf - α活化的抑制作用分别为21% ~ 93%和36% ~ 82%。单独使用IL-6对M φ的活力和亚马孙乳杆菌的细胞内生长没有影响。在感染前24或48小时加入IL-6并使用ifn - γ或tnf - α治疗时，对M - phi活化的阻断作用最大。此外，针对IL-6的单抗可以消除IL-6的抑制活性。同样，IL-6预处理抑制了IL-3、粒细胞-单核细胞- csf （GM-CSF）和IL-1 β对M- phi抗利什曼原虫能力的激活。由于细胞因子诱导抗利什曼原虫活性与氧化能力增强有关，因此我们评估了IL-6在这一机制中的作用。预处理IL-6下调tnf - α (25 ng/mL)以剂量和时间依赖的方式增强M phi的氧化能力。GM-CSF和IL-3的氧化能力也有类似的下降，但ifn - γ没有。此外，ng -单甲基- l-精氨酸（一种一氧化氮合酶抑制剂）对抗利什曼原虫活性的ifn - γ和tnf - α激活没有影响，并且从培养上清中不能可靠地检测亚硝酸盐/硝酸盐。这些发现表明，IL-6通过抑制氧依赖性和未明确的氧非依赖性机制，下调了细胞因子对M φ抗利什曼原虫能力的激活。
IL-6 is a cytokine synthesized by T cells and macrophages (M phi). It has pleiotropic effects on diverse cell types and is recognized for its "pro-inflammatory" properties. In mice, IL-4, IL-5, IL-6, and IL-10 are produced by Th-2 cells. Because IL-10 suppresses Th-1 clones, and IL-4 broadly deactivates M phi, experiments were carried out to investigate the in vitro effects of recombinant human IL-6 on cytokine activation of human M phi. Pretreatment with IL-6 induced a dose- and time-dependent suppression of IFN-gamma (1000 U/mL) and TNF-alpha (25 ng/mL) activation of M phi for the killing of L. amazonensis. At doses greater than 0.1 to 100 ng/mL, IL-6 inhibited IFN-gamma and TNF-alpha activation by 21 to 93% and 36 to 82%, respectively. IL-6 alone had no effect on M phi viability and intracellular L. amazonensis growth. Blockade of M phi activation was greatest when IL-6 was added 24 or 48 h before infection and treatment with IFN-gamma or TNF-alpha. Furthermore, mAb against IL-6 abrogated the inhibitory activity of IL-6. Similarly IL-6 pretreatment suppressed M phi activation for antileishmanial capacity by IL-3, granulocyte-monocyte-CSF (GM-CSF) and IL-1 beta. Because cytokine induction of antileishmanial activity is associated with enhancement of oxidative capacity, the effect of IL-6 on this mechanism was evaluated. Pretreatment with IL-6 down-modulated TNF-alpha (25 ng/mL) enhancement of M phi oxidative capacity in a dose- and time-dependent manner. A similar depression of oxidative capacity was observed for GM-CSF and IL-3 but not for IFN-gamma. Furthermore, NG-monomethyl-L-arginine (a nitric oxide synthase inhibitor) had no effect on IFN-gamma and TNF-alpha activation of antileishmanial activity and nitrites/nitrates were not reliably assayed from M phi culture supernatants. These findings suggest that IL-6 down-modulates cytokine activation of M phi antileishmanial capacity by inhibiting oxygen-dependent and undefined oxygen-independent mechanisms.