在小鼠哮喘模型中能很好地研究辅助性T细胞2型(Th2)细胞因子(如IL-5和IL-3)在调节嗜酸性粒细胞及哮喘其它关键性特征中的作用。但是,实验小鼠感染蛲虫会使模型研究的有效性受到影响。苯并咪唑的衍生物-芬苯达唑(FBZ)常用于蛲虫感染的治疗。但是FBZ对小鼠Th2相关疾病的作用了解较少。
在该研究中我们发现,在宫内和断奶后给予含FBZ饮食的小鼠,肺内嗜酸性粒细胞、抗原特异性IgG1下降,且Th2细胞的细胞因子反应减弱。体外对过敏小鼠纵隔淋巴结采用FBZ处理,能显著降低细胞增殖、IL-5和IL-13的产生以及CD4+T细胞和CD19+B细胞表面早期淋巴细胞活化标记物CD69的表达。此外,若断奶前即对过敏小鼠采用FBZ治疗,4周后嗜酸性粒细胞和Th2细胞反应下降。体内体外实验均显示FBZ能调节Th2细胞的反应强度。
(林江涛 审校)
Cai Y, Zhou J, Webb DC. Immunol Cell Biol. 2009 Jul 21. [Epub ahead of print]
Treatment of mice with fenbendazole attenuates allergic airways inflammation and Th2 cytokine production in a model of asthma.
Cai Y, Zhou J, Webb DC.
Immunology Program, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Mouse models have provided a significant insight into the role of T-helper (Th) 2 cytokines such as IL-5 and IL-13 in regulating eosinophilia and other key features of asthma. However, the validity of these models can be compromised by inadvertent infection of experimental mouse colonies with pathogens such as oxyurid parasites (pinworms). While the benzimidazole derivative, fenbendazole (FBZ), is commonly used to treat such outbreaks, the effects of FBZ on mouse models of Th2 disease are largely unknown. In this investigation, we show that mice fed FBZ-supplemented food during the in utero and post-weaning period developed attenuated lung eosinophilia, antigen-specific IgG1 and Th2 cytokine responses in a model of asthma. Treatment of the mediastinal lymph node cells from allergic mice with FBZ in vitro attenuated cell proliferation, IL-5 and IL-13 production and expression of the early lymphocyte activation marker, CD69 on CD4(+) T cells and CD19(+) B cells. In addition, eosinophilia and Th2 responses remained attenuated after a 4-week withholding period in allergic mice treated preweaning with FBZ. Thus, FBZ modulates the amplitude of Th2 responses both in vivo and in vitro.