Floris Ilaria, Chenuet Pauline, Togbe Dieudonnée, Volteau Christelle, Lejeune Beatrice
Preclinical & Clinical Development and Regulatory Affairs, Labo'Life France, Nantes, France.
ArtImmune, Orléans, France.
Dose Response. 2020 Mar 24;18(1):1559325820914092. doi: 10.1177/1559325820914092. eCollection 2020 Jan-Mar.
In this study, we evaluated the efficacy of a micro-immunotherapy medicine (MIM), 2LALERG, in a preclinical model of allergic respiratory disease sensitized with birch pollen extract (BPE). BALB/c mice were immunized with BPE, or saline solution, and were then challenged. Micro-immunotherapy medicine pillules were diluted in water, and 3 doses (0.75; 1.5; 3 mg/mouse) were tested and compared to vehicle control (3 mg/mouse). Treatments and vehicle were orally administered by gavage for 10 days. Micro-immunotherapy medicine (0.75 mg/mouse) reduced the number of total cells as well as the levels of interleukin (IL)-13 in bronchoalveolar lavage fluid (BALF) compared to vehicle control. Eosinophils in BALF tended to be lower compared to vehicle group, and the difference is close to significance. Histological analysis in the lungs confirms a moderate effect of MIM (0.75 mg/mice) on inflammatory infiltration and mucus production. Serum levels of IL-5 in MIM (0.75 mg/mouse)-treated mice were lower compared to vehicle; IL-4 levels tended to be lower too. Total immunoglobulin E (IgE) decreased in serum of MIM (1.5 and 0.75 mg/mouse) groups compared to vehicle control. Micro-immunotherapy medicine exerted the highest effect at the lowest dose tested. Micro-immunotherapy medicine resolved the local and systemic inflammation, even if partially, in a model of pollen-induced, IgE-mediated inflammation.
在本研究中，我们评估了一种微免疫疗法药物（MIM）——2LALERG，在桦树花粉提取物（BPE）致敏的变应性呼吸道疾病临床前模型中的疗效。用BPE或生理盐水对BALB/c小鼠进行免疫，然后进行激发试验。将微免疫疗法药丸在水中稀释，测试了3种剂量（0.75；1.5；3mg/小鼠），并与赋形剂对照（3mg/小鼠）进行比较。通过灌胃口服给予治疗药物和赋形剂，持续10天。与赋形剂对照相比，微免疫疗法药物（0.75mg/小鼠）减少了支气管肺泡灌洗液（BALF）中的总细胞数以及白细胞介素（IL）-13水平。与赋形剂组相比，BALF中的嗜酸性粒细胞数量有降低趋势，差异接近显著。肺部组织学分析证实MIM（0.75mg/小鼠）对炎症浸润和黏液分泌有中度作用。与赋形剂相比，用MIM（0.75mg/小鼠）治疗的小鼠血清中IL-5水平较低；IL-4水平也有降低趋势。与赋形剂对照相比，MIM（1.5和0.75mg/小鼠）组血清中的总免疫球蛋白E（IgE）降低。微免疫疗法药物在测试的最低剂量下发挥了最大作用。在花粉诱导的、IgE介导的炎症模型中，微免疫疗法药物即使只是部分地缓解了局部和全身炎症。
