Intralymphatic treatment of flagellin-ovalbumin mixture reduced allergic inflammation in murine model of allergic rhinitis.

ABSTRACT

BACKGROUND: Bacterial flagellin, a Toll-like receptor 5 agonist, is used as an adjuvant for immunomodulation. In this study, we aimed to evaluate the effect and its mechanism following intralymphatic administration of OVA-flagellin (FlaB) mixture in the mouse model of allergic rhinitis. MATERIALS AND METHODS: BALB/c mice were sensitized with OVA and treated with an OVA-FlaB mixture via intranasal, sublingual, and intralymphatic routes to evaluate the effect of each treatment. Several parameters for allergic inflammation and its underlying mechanisms were then evaluated. RESULTS: Intralymphatic injection of the OVA-FlaB mixture reduced symptom scores, eosinophil infiltration in the nasal mucosa, and total and OVA-specific IgE levels more significantly than intranasal and sublingual administration. Systemic cytokine (IL-4, IL-5, IL-6, IL-17, and IFN-γ) production and local cytokine (IL-4 and IL-5) production were also reduced significantly after intralymphatic injection with OVA-FlaB. Double intralymphatic injection of the mixture was more effective than single injection. Moreover, the expression of innate cytokines such as IL-25 and IL-33 in nasal epithelial cells was reduced, and the expression of chemokines such as CCL24 (eotaxin-2), CXCL1, and CXCL2 was decreased in the nasal mucosa, suggesting the underlying mechanism for intralymphatic administration of the OVA-FlaB mixture. CONCLUSION: Intralymphatic administration of an OVA-FlaB mixture was more effective in alleviating allergic inflammation than intranasal and sublingual administration in a mouse model of allergic rhinitis. This effect may be attributed to the reduced expression of innate cytokines and chemokines. This treatment modality can be considered as a new therapeutic method and agent.