Yang C, Chen N, Tang X L, Qian X H, Cai C P
Department of Otolaryngology & Head and Neck Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Huangpu District, Shanghai, China.
School of Biomedical Engineering, Shanghai Jiao Tong University, Xuhui District, Shanghai, China.
J Biol Regul Homeost Agents. 2021 Mar-Apr;35(2):571-581. doi: 10.23812/20-615-A.
Both interleukin (IL)-33 and IL-25 induce Th2-type cytokine production by various cell types, suggesting that they may contribute to development of allergic disorders, however, the immunomodulatory effects of IL-33 and IL-25 in ovalbumin (OVA)-induced allergic rhinitis (AR) remain unclear. In the present study, anti-IL-33 and anti-IL-25 Abs were administrated intranasally during rechallenge in OVA-induced AR. Immunomodulatory effects were evaluated by measuring nasal rubbing, sneezing occurrence, serum OVA-specific antibodies, Th2 immune responses, neutrophil, eosinophil and mast cell recruitment into the nasal mucosa. We found that treatment with anti-IL-33 Ab markedly reduced nasal rubbing, sneezing events, Th2 immune responses, serum OVA-specific IgE and IgG1 levels, mucosal neutrophil, eosinophil and mast cell infiltration. In contrast, the effect of IL-25 antagonism was limited to attenuating the Th2 immune responses, and neutrophil and eosinophil infiltration. These observations indicate that IL-33 and IL-25 play a pathogenic role in an established AR mouse model, with a greater contribution of IL-33 than IL-25. Our findings suggest that IL-33 neutralization may be a potential approach for treatment of AR.
白细胞介素（IL）-33和IL-25均可诱导多种细胞类型产生Th2型细胞因子，提示它们可能参与过敏性疾病的发生发展。然而，IL-33和IL-25在卵清蛋白（OVA）诱导的变应性鼻炎（AR）中的免疫调节作用仍不清楚。在本研究中，在OVA诱导的AR再次激发过程中经鼻给予抗IL-33和抗IL-25抗体。通过测量鼻摩擦、喷嚏发作次数、血清OVA特异性抗体、Th2免疫反应、中性粒细胞、嗜酸性粒细胞和肥大细胞向鼻黏膜的募集来评估免疫调节作用。我们发现，抗IL-33抗体治疗可显著减少鼻摩擦、喷嚏发作次数、Th2免疫反应、血清OVA特异性IgE和IgG1水平、黏膜中性粒细胞、嗜酸性粒细胞和肥大细胞浸润。相比之下，IL-25拮抗作用仅限于减弱Th2免疫反应以及中性粒细胞和嗜酸性粒细胞浸润。这些观察结果表明，IL-33和IL-25在已建立的AR小鼠模型中起致病作用，且IL-33的作用大于IL-25。我们的研究结果提示，中和IL-33可能是治疗AR的一种潜在方法。
