Therapeutic effect of low-dose IL-18 combined with IL-10 on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of Th2 responses
Therapeutic effect of low-dose IL-18 combined with IL-10 on collagen-induced arthritis by down-regulation of inflammatory and Th1 responses and induction of Th2 responses
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DOI：
10.1007/s00296-008-0732-3
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发表时间：
2009-04-01
影响因子：
4
通讯作者：
Wang, Xiaoyan
中科院分区：
文献类型：
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作者：
Dai, Qiaomei;Li, Yang;Wang, Xiaoyan
为了研究白细胞介素18（IL-18）的抗炎或多效性免疫调节作用，将IL-18沿着或与IL-10、IL-4或IL-12联合施用于胶原诱导的关节炎（CIA）小鼠。IL-18治疗沿着对发作或建立的CIA小鼠没有治疗效果。然而，低剂量IL-18与IL-10的联合治疗改善了疾病进展。与对照组相比，IL-18/IL-10治疗组滑膜组织中Th 1细胞因子的表达显著抑制，而Th 2细胞因子的表达上调。有趣的是，IL-18受体（IL-18 R）α表达通过治疗下调。根据Th 2应答的发展，治疗组中加塔-3 mRNA表达显著增加。我们的研究结果表明，低剂量IL-18与IL-10的联合治疗可以预防CIA的发展，这可能不仅通过IL-18/IL-18 R α信号转导抑制Th 1应答介导，而且通过加塔-3依赖性机制诱导抗炎介质介导。
To investigate the anti-inflammatory or pleiotropic immunomodulatory role of interleukin-18 (IL-18), collagen-induced arthritis (CIA) mice were administrated with IL-18 along or in combination with IL-10, IL-4 or IL-12. IL-18 treatment along had no therapeutic effect on onset or established CIA mice. However, the combined treatment of low-dose IL-18 with IL-10 ameliorated the disease progression. Th1 cytokine expression was significantly inhibited, whereas Th2 cytokine expression was up-regulated in the synovial tissue by the IL-18/IL-10 treatment when compared with that in control group. Interestingly, IL-18 receptor (IL-18R) alpha expression was down-regulated by the treatment. According to the development of Th2 responses, GATA-3 mRNA expression was significantly increased in the treatment group. Our results indicated that combined treatment of low-dose IL-18 with IL-10 can prevent the development of CIA, which may be mediated not only by inhibiting Th1 responses through IL-18/IL-18R alpha signaling, but also by inducing anti-inflammatory mediators through a GATA-3-dependent mechanism.