Immunomodulatory effects of IL-33 and IL-25 in an ovalbumin-induced allergic rhinitis mouse model.

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.