Dual effects of interleukin-10 on natural killer cells and monocytes and the implications for adult-onset Still's disease
Dual effects of interleukin-10 on natural killer cells and monocytes and the implications for adult-onset Still's disease
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DOI：
10.55563/clinexprheumatol/2vdem0
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发表时间：
2021-01-01
影响因子：
3.7
通讯作者：
Mimura, T.
中科院分区：
文献类型：
--
作者：
Aizaki, Y.;Yazawa, H.;Mimura, T.
Objective.我们比较了成人斯蒂尔病（AOSD）患者和健康对照者血清中多种细胞因子的水平，以评估体液因素对自然杀伤（NK）细胞和单核细胞的影响。我们使用基于微珠的多重免疫测定法定量患者血清中10种细胞因子的水平，使用ELISA法沿着白细胞介素（IL-）18。然后，我们从健康志愿者的外周血单个核细胞（PBMC）中分选NK细胞和单核细胞，在存在或不存在细胞因子的情况下体外培养它们，并分析培养上清液。AOSD患者血清中升高的细胞因子主要为IL-6和IL-18。当NK细胞与细胞因子和IL-10一起培养时，IL-10和IL-18的组合基本上诱导干扰素（IFN-γ）。IL-6对NK细胞几乎没有影响，可能是因为它们几乎不表达IL-6受体和糖蛋白130（gp 130）。IFN-γ诱导单核细胞产生IL-1 β、IL-6和肿瘤坏死因子（TNF-α），而IL-10抑制这些促炎细胞因子的诱导。IL-10显然对NK细胞（刺激）和单核细胞（抑制）具有双重作用。更好地理解细胞因子网络的作用将有助于阐明AOSD的发病机制。
Objective. We compared the serum levels of multiple cytokines in patients with adult-onset Still's disease (AOSD) and healthy controls to assess the effects of humoral factors on natural killer (NK) cells and monocytes.Methods. We quantified the serum levels of 10 cytokines in the patients using bead-based multiplex immunoassays, along with interleukin (IL-)18 using ELISA. We then sorted NK cells and monocytes from the peripheral blood mononuclear cells (PBMCs) of healthy volunteers, cultured them in the presence or absence of cytokines that were detected in some or all of the serum samples from the AOSD patients and their combinations in vitro, and analysed the culture supernatant.Results. IL-6 and IL-18 were the main cytokines increased in the serum of AOSD patients. When NK cells were cultured with the cytokines and IL-10, the combination of IL-10 and IL-18 substantially induced interferon (IFN-)gamma. IL-6 had little effect on NK cells, probably because they barely expressed the IL-6 receptor and glycoprotein 130 (gp130). IFN-gamma induced monocytes to produce IL-1 beta, IL-6 and tumour necrosis factor (TNF-)alpha whereas IL-10 inhibited the induction of these proinflammatory cytokines.Conclusion. IL-10 evidently has dual effects on NK cells (stimulation) and on monocytes (inhibition). Better understanding the roles of the cytokine network would shed light on the pathogenesis of AOSD.