局部 IL-10 替代疗法对小鼠的类固醇不敏感哮喘有效
2022/09/20
摘要
背景：严重哮喘患者的亚组分析显示痰中嗜酸性粒细胞和/或中性粒细胞显著增加，对皮质类固醇不敏感。先前的报告表明，外源性给予抗炎细胞因子白细胞介素（IL）-10对嗜酸性粒细胞和嗜中性粒细胞迁移到组织中均具有负调节作用。本研究的目的是阐明在激素不敏感的小鼠模型中，气管内给予IL-10是否抑制哮喘反应。
方法：卵清蛋白（OVA）致敏BALB/c小鼠气管内用500µg/只，用OVA激发四次。在多次激发期间给予地塞米松（1mg/kg，腹腔内）或IL-10（25ng/小鼠，气管内）。在第四次激发后，评估肺中白细胞的数量、细胞间粘附分子-1（ICAM-1）、血管细胞粘附分子-1（VCAM-1）和IL-10受体的表达，以及气道重塑和高反应性的情况。
结果：与我们之前的研究一致，地塞米松几乎没有抑制气道重塑和高反应性。尽管气管内给予IL-10不影响气道重塑的发展，但嗜酸性粒细胞和中性粒细胞的浸润以及气道高反应性的发展受到显著抑制。此外，IL-10的使用显著减少了表达IL-10受体1的ICAM-1+和VCAM-1+肺血管内皮细胞的数量，即使肺中嗜酸性细胞和嗜中性细胞因子的产生都没有受到抑制。
结论：因此，IL-10可通过抑制ICAM-1+和VCAM- 1+肺血管内皮细胞增殖，抑制嗜酸性粒细胞和中性粒细胞浸润，从而抑制激素不敏感哮喘小鼠气道高反应性。IL-10替代疗法可能对治疗激素不敏感哮喘有临床价值。
(中日友好医院呼吸与危重症医学科 万静萱 摘译 林江涛 审校)
(International immunopharmacology. 2022 Sep;110:109037. doi:10.1016/j.intimp.2022.109037.)
Local IL-10 replacement therapy was effective for steroid-insensitive asthma in mice.
Masaya Matsuda, Miki Inaba, Junpei Hamaguchi,
Abstrast
Background: Subgroups of patients with severe asthma showing marked increases in sputum eosinophils and/or neutrophils are insensitive to corticosteroids. Previous reports have shown that exogenous administration of an anti-inflammatory cytokine, interleukin (IL)-10 negatively regulated both eosinophilic and neutrophilic migration into tissues. The objective of this study was to elucidate whether intratracheal IL-10 administration suppresses asthmatic responses in a steroid-insensitive model of mice.
Methods: Ovalbumin (OVA)-sensitized BALB/c mice were intratracheally challenged with OVA at 500 μg/animal four times. Dexamethasone (1 mg/kg, intraperitoneal) or IL-10 (25 ng/mouse, intratracheal) was administered during the multiple challenges. The number of leukocytes, expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and IL- 10 receptor in the lung, and the development of airway remodeling and hyperresponsiveness were evaluated after the fourth challenge.
Results: Consistent with our previous study, dexamethasone hardly suppressed the development of airway remodeling and hyperresponsiveness. Although intratracheal IL-10 administration did not affect the development of airway remodeling, the infiltration of eosinophils and neutrophils, and the development of airway hyperresponsiveness were significantly inhibited. Moreover, IL-10 administration significantly decreased the numbers of ICAM-1+ and VCAM-1+ pulmonary vascular endothelial cells, which express IL-10 receptor 1, even though neither production of eosinophilic nor neutrophilic cytokines in the lung was inhibited.
Conclusion: Therefore, IL-10 can suppress eosinophil and neutrophil infiltration by inhibiting the proliferation of ICAM-1+ and VCAM- 1+ pulmonary vascular endothelial cells, resulting in inhibition of airway hyperresponsiveness in steroidinsensitive asthmatic mice. IL-10 replacement therapy may be clinically useful for the treatment of steroidinsensitive asthma.
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