IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation
IL-10 controls Th2-type cytokine production and eosinophil infiltration in a mouse model of allergic airway inflammation
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DOI：
10.1016/j.imbio.2010.12.003
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发表时间：
2011-07-01
期刊：
影响因子：
2.8
通讯作者：
Kitasato, Hidero
中科院分区：
文献类型：
--
作者：
Kosaka, Shinichiro;Tamauchi, Hidekazu;Kitasato, Hidero
白细胞介素-10最初被描述为抑制鼠Th 1克隆产生细胞因子的因子。最近的研究表明，IL-10还可以下调Th 2克隆及其I1-4和IL-5的产生。由于其免疫抑制特性，11-10已被建议作为过敏性炎症和哮喘的潜在疗法。然而，IL-10在体内的病理生理学作用尚未明确阐明。我们研究了IL-10给药对IgE、细胞因子和过敏原诱导的Th 2细胞因子产生的影响以及对嗜酸性粒细胞炎症的影响。我们通过将加塔-3转基因小鼠与卵清蛋白（OVA）特异性TCR转基因小鼠杂交，建立了加塔-3/TCR双转基因（加塔-3[TCR-Tg）小鼠;然后使用腹腔内注射吸附到明矾上的OVA致敏这些小鼠，并使用气管内滴注过敏原进行攻击。用OVA和明矾致敏的加塔-3/TCR-Tg小鼠，在吸入OVA前注射C57-IL-10细胞，可使支气管肺泡灌洗液（BALF）中的I1-5、IL-13和I1-4水平降低40-85%，嗜酸性粒细胞减少70%（P< 0.03）。这些结果表明，IL-10起着重要的作用，下游的炎症级联反应的Th 2抗原反应和BALF嗜酸性粒细胞和细胞因子的产生在小鼠哮喘模型的发展。动物模型中的这些免疫抑制特性表明11-10可能是治疗过敏性炎症的潜在临床疗法。(C)2011年Elsevier GmbH。All rights reserved.
Interleukin-10 was originally described as a factor that inhibits cytokine production by murine Th1 clones. Recent studies have since shown that IL-10 can also downregulate Th2 clones and their production of I1-4 and IL-5. Because of its immuno-suppressive properties, 11-10 has been suggested as a potential therapy for allergic inflammation and asthma. However, the pathophysiological role of IL-10 in vivo has not been clearly elucidated. We investigated the effects of IL-10 administration on the production of IgE, cytokine and allergen-induced Th2 cytokine production as well as its effects on eosinophilic inflammation. We established GATA-3/TCR double transgenic (GATA-3[TCR-Tg) mice by crossing GATA-3 transgenic mice with ovalbumin (OVA)-specific TCR transgenic mice; these mice were then sensitized using an intraperitoneal injection of OVA adsorbed to alum and challenged with the intratracheal instillation of an allergen. When GATA-3/TCR-Tg mice sensitized with OVA and alum were injected with C57-IL-10 cells before OVA inhalation, the levels of I1-5, IL-13, and I1-4 decreased by 40-85% and number of eosinophils decreased by 70% (P< 0.03) in the murine bronchoalveolar lavage fluid (BALF). These results suggest that IL-10 plays an important role downstream of the inflammatory cascade in the Th2 response to antigens and in the development of BALF eosinophilia and cytokine production in a murine model of asthma. These immunosuppressive properties in animal models indicate that 11-10 could be a potential clinical therapy for the treatment of allergic inflammation. (C) 2011 Elsevier GmbH. All rights reserved.