Background: Sublingual immunotherapy (SLIT) is a safe and effective treatment for allergic rhinitis (AR). However, many issues regarding SLIT remain to be resolved, including the optimal timing of administration. This study investigated the effect of time of day on SLIT efficacy with the goal of optimizing the therapeutic outcome. Methods: We performed prophylactic SLIT at different times of day (10 a.m. or 10 p.m.) in 2 mouse models of AR: an ovalbumin (OVA)-induced AR model and Cry j 1-induced AR model, and compared the effects. Results: In the OVA-induced AR model, mice sublingually receiving OVA at 10 a.m. exhibited a greater decrease in total and OVA-specific IgE levels than mice treated at 10 p.m. In addition, mice treated at 10 a.m. exhibited reductions in OVA-specific IL-4, IL-10, and IL-13 production by splenocytes relative to mice treated at 10 p.m. Furthermore, we observed a more efficient capture of sublingually administered OVA in submandibular lymph nodes at 10 a.m. than at 10 p.m. in mice. Similar results were observed in the Cry j 1-induced AR model using Japanese cedar pollen extract for SLIT. Conclusions: Given the allergen-specific antibody and T cell responses, we suggest that SLIT may be more effective in the resting phase than in the active phase (note that mice are nocturnal animals). Thus, we propose that a chronotherapeutic approach should be considered for SLIT to maximize its effectiveness.

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