Brimnes J, Kildsgaard J, Jacobi H, Lund K
Department of Experimental Immunology, ALK-Abelló A/S, Hoersholm, Denmark.
Clin Exp Allergy. 2007 Apr;37(4):488-97. doi: 10.1111/j.1365-2222.2006.02624.x.
Sublingual immunotherapy (SLIT) is a clinically effective treatment in both pollen and house dust mite-induced rhinitis and asthma. However, the mechanisms by which this is accomplished are not clear.
The objective of the current study was to establish a mouse model of rhinitis in order to study the effect and mechanisms of SLIT.
Mice were sensitized by intraperitoneal injections of alum-adsorbed Phleum pratense extract. Sensitized mice were SLIT-treated and subsequently challenged intranasally and analysed for clinical symptoms, antibody levels, eosinophilia and T cell response.
Intranasal challenge of sensitized mice led to the development of rhinitis characterized by significantly increased sneezing and influx of eosinophils into the nose. Levels of specific IgE were fivefold increased in nasopharyngeal lavage (NAL) fluid and more than doubled in serum. Furthermore, a T-helper type 2 (Th2) like T cell response was observed in local draining lymph nodes. SLIT treatment of sensitized mice reduced sneezing, eosinophilia and IgE levels in the NAL by more than 50%. Moreover, serum levels of IgE and IgG1 as well as T cell response in the draining lymph nodes were also significantly reduced. Treatment for a shorter time or with a lower dose only led to minor reductions of the clinical and immunological parameters, indicating that the effect of SLIT is time and dose dependent.
In the present study, we have established a mouse model displaying the hallmarks of allergic rhinitis using a clinically relevant allergen. Using this model, we have demonstrated that SLIT treatment is able to reduce allergic symptoms in a time- and dose-dependent manner.
舌下免疫疗法(SLIT)是治疗花粉和屋尘螨引起的鼻炎及哮喘的一种临床有效疗法。然而,其作用机制尚不清楚。
本研究旨在建立一种鼻炎小鼠模型,以研究舌下免疫疗法的效果及机制。
通过腹腔注射明矾吸附的梯牧草提取物使小鼠致敏。对致敏小鼠进行舌下免疫疗法治疗,随后进行鼻内激发,并分析其临床症状、抗体水平、嗜酸性粒细胞增多情况及T细胞反应。
对致敏小鼠进行鼻内激发会导致鼻炎的发生,其特征为打喷嚏显著增加以及嗜酸性粒细胞流入鼻腔。鼻咽灌洗液(NAL)中特异性IgE水平增加了五倍,血清中则增加了一倍多。此外,在局部引流淋巴结中观察到了类似辅助性T细胞2(Th2)的T细胞反应。对致敏小鼠进行舌下免疫疗法治疗可使打喷嚏、嗜酸性粒细胞增多情况以及NAL中的IgE水平降低50%以上。此外,血清中的IgE和IgG1水平以及引流淋巴结中的T细胞反应也显著降低。较短时间或较低剂量的治疗仅导致临床和免疫参数略有降低,这表明舌下免疫疗法的效果具有时间和剂量依赖性。
在本研究中,我们使用一种临床相关变应原建立了一种具有变应性鼻炎特征的小鼠模型。利用该模型,我们证明了舌下免疫疗法能够以时间和剂量依赖性方式减轻变应性症状。