Transient Induction of Salivary SIgA by Intranasal Hinokitiol in Middle-Aged Mice

This study aimed to determine whether intranasal hinokitiol modulates short-term salivary secretory IgA (SIgA) secretion dynamics and IgA antibody-forming cell (AFC) activity in the submandibular glands of aged mice, a model of age-associated mucosal immune decline. Aged BALB/c mice received intranasal hinokitiol (50 μg) once weekly for 4 weeks. Saliva was collected on days 0, 7, 14, and 21 at baseline, 0.5 h, 1.5 h, 3 h, and 6 h after each administration. SIgA levels were measured using an enzyme-linked immunosorbent assay. On day 21, IgA AFCs were enumerated using an enzyme-linked immunosorbent spot assay, and their viability and proliferative activity were assessed using the MTT assay. Salivary SIgA rose transiently after each dose, peaking at 1.5 h and returning to baseline by 6 h. By day 21, baseline SIgA secretion was significantly higher than at day 0, indicating a cumulative effect. IgA AFCs were unchanged in number, but viability and proliferation increased at 0.5 and 1.5 h, coinciding with SIgA peaks. Flow cytometry revealed significant expansion of B220+CD38+ memory B-cells; B220+CD138+ plasma cells were unaffected. Intranasal hinokitiol transiently enhances salivary SIgA secretion in aged mice, likely through short-term modulation of salivary gland immune activity. This non-invasive approach may aid mucosal defense in aging populations. These findings suggest that intranasal HNK may represent a novel non-invasive approach for enhancing mucosal immune function during aging and may provide a basis for future preventive strategies against oral and respiratory infections.