Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Yuta Clinic, Tsu, Japan.
Allergol Int. 2019 Jan;68(1):82-89. doi: 10.1016/j.alit.2018.07.008. Epub 2018 Aug 27.
The development of methods to predict the clinical effectiveness of sublingual immunotherapy (SLIT) for allergic diseases is a crucial matter. We sought to determine whether whole saliva, which is the first body component that contacts allergen extracts during SLIT, is associated with the clinical effectiveness of SLIT in Japanese cedar pollinosis.
Blood monocytes or monocytic THP-1 cells were cultured in the presence or absence of either whole saliva or pure saliva with or without treatments including filtration and blockade of TLR2 and/or TLR4 signaling. IL-10 levels in the supernatants were then measured. Whole saliva-induced IL-10 production by THP-1 cells was compared between asymptomatic and disease-onset patients during peak pollen dispersal after SLIT.
Both monocytes and THP-1 cells produced substantial amounts of IL-10 in response to whole saliva. IL-10 production was significantly reduced in response to pure saliva and 0.2 μm-filtered saliva. Simultaneous treatment with polymyxin B and TL2.1, a neutralizing antibody against TLR2, also reduced IL-10 production. IL-10 levels produced by THP-1 cells in response to whole saliva collected prior to SLIT were significantly higher in asymptomatic patients determined by symptom-medication scores than disease-onset patients following SLIT. Such differences were not seen in saliva collected 3 months after the initiation of SLIT or saliva collected during peak pollen dispersal.
Our results provide a basis for why the sublingual route is effective and preferable in allergen immunotherapy. Saliva-induced IL-10 levels produced by THP-1 cells may be a predictive marker for clinical remission after SLIT.
开发预测舌下免疫疗法(SLIT)治疗过敏性疾病临床疗效的方法至关重要。我们旨在确定在日本杉花粉症患者中,作为 SLIT 过程中首先与变应原提取物接触的第一身体成分的全唾液是否与 SLIT 的临床疗效相关。
在存在或不存在全唾液或纯唾液的情况下培养血液单核细胞或单核细胞 THP-1 细胞,同时进行包括过滤和 TLR2 和/或 TLR4 信号转导阻断的处理。然后测量上清液中的 IL-10 水平。比较 SLIT 后花粉散发高峰期无症状和发病患者的全唾液诱导 THP-1 细胞产生的 IL-10。
单核细胞和 THP-1 细胞对全唾液均产生大量的 IL-10。纯唾液和 0.2μm 过滤唾液的反应 IL-10 产量明显降低。同时用多粘菌素 B 和 TL2.1(TLR2 的中和抗体)处理也降低了 IL-10 的产生。通过症状药物评分确定无症状患者的 SLIT 前采集的全唾液刺激 THP-1 细胞产生的 IL-10 水平明显高于 SLIT 后发病患者。在 SLIT 开始后 3 个月采集的唾液或在花粉散发高峰期采集的唾液中未观察到这种差异。
我们的结果为为什么舌下途径在变应原免疫治疗中是有效且优选的提供了依据。THP-1 细胞产生的由唾液诱导的 IL-10 水平可能是 SLIT 后临床缓解的预测标志物。