Department of Internal Medicine, Seoul National University, 28 Yongondong, Chongno-gu, Seoul, 110-744, Republic of Korea.
J Clin Immunol. 2010 May;30(3):459-64. doi: 10.1007/s10875-009-9363-z. Epub 2010 Jan 14.
Accumulating evidence indicates that cells expressing Toll-like receptors (TLRs) play an important role in allergic diseases. The authors undertook this study to explore the hypothesis that TLR-mediated inflammatory signals are important from the perspective of asthma management.
The expressions of TLR1, TLR2, TLR3, TLR4, TLR6, and TLR9 and levels of pro-inflammatory cytokines (TNF-alpha, IL-1beta, IL-6, IL-8, and IFN-gamma) on the peripheral blood mononuclear cells (PBMCs) of 36 stable asthmatics on treatment (the on-treatment group), 15 asthmatics (the treatment-naïve group) before and after a 7-day course of oral prednisolone (30 mg/day), and on the PBMCs of 15 healthy controls were measured after in vitro stimulation using TLR-specific ligands.
In the on-treatment group, TLR1, TLR2, TLR6, and TLR9 expressions on PBMCs were significantly different between asthmatics and controls. And the expression of TLR4 on PBMCs and TNF-alpha production stimulated by lipopolysaccharide (LPS), were significantly higher in mild to moderate than in severe asthmatics. Interestingly, in the treatment-naïve group, short-term prednisolone significantly increased LPS-induced TNF-alpha and IFN-gamma productions by PBMCs.
TLR-mediated inflammatory signals contribute to the development and severity of asthma and are not reduced by glucocorticoid treatment, which suggests that a TLR-specific antagonist and glucocorticoid are required for the effective control of airway inflammation in asthmatics.
越来越多的证据表明表达 Toll 样受体 (TLR) 的细胞在过敏性疾病中发挥重要作用。作者开展这项研究旨在从哮喘管理的角度探索 TLR 介导的炎症信号很重要的假说。
作者检测了 36 名经治疗的稳定期哮喘患者(治疗组)、15 名治疗前哮喘患者(治疗前组)和 15 名健康对照者外周血单个核细胞(PBMC)中 TLR1、TLR2、TLR3、TLR4、TLR6 和 TLR9 的表达以及促炎细胞因子(TNF-α、IL-1β、IL-6、IL-8 和 IFN-γ)水平,这些患者均接受了为期 7 天的口服泼尼松龙(30mg/天)治疗,并用 TLR 特异性配体进行体外刺激。
治疗组中,哮喘患者与健康对照者的 PBMC 中 TLR1、TLR2、TLR6 和 TLR9 的表达存在显著差异。而且,中重度哮喘患者的 PBMC 中 TLR4 表达和脂多糖(LPS)刺激产生的 TNF-α明显高于轻度哮喘患者。有趣的是,治疗前组中,短期泼尼松龙治疗明显增加了 LPS 诱导的 PBMC 产生 TNF-α和 IFN-γ。
TLR 介导的炎症信号有助于哮喘的发生和严重程度,糖皮质激素治疗不能降低这些信号,这表明哮喘患者气道炎症的有效控制需要 TLR 特异性拮抗剂和糖皮质激素联合治疗。