Synergistic Exacerbation of Allergic Inflammation by Combined Exposure to Air-pollutants in a Murine Model of Allergic Rhinitis

Allergic rhinitis (AR) is a chronic nasal mucosal inflammation triggered by environmental allergens. Although its pathophysiology has been well studied, the effects of environmental aggravating factors-especially combined pollutant exposure-are not fully understood. This study aimed to evaluate the impact of coexposure to PM2.5, formaldehyde, and zinc on allergic inflammation in a murine model of AR and to characterize the associated immunological and histopathological responses. Female BALB/c mice were sensitized with ovalbumin (OVA) and challenged intranasally to induce allergic rhinitis. On days 21-24, mice were exposed to PM2.5, formaldehyde, and zinc either individually or in combination with OVA. Allergic symptoms were assessed through behavioral observation, and immune responses were evaluated by analyzing nasal and bronchoalveolar lavage fluids (NALF and BALF), serum immunoglobulin levels, nasal histology, and cytokine profiles. Combined exposure to PM2.5, formaldehyde, and zinc significantly enhanced allergic inflammation compared to single exposures. Coexposure to PM2.5 and zinc resulted in synergistic increases in total and OVA-specific immunoglobulin E(IgE) levels, eosinophilic infiltration, nasal rubbing, and Th2/Th17 cytokines in NALF and BALF. Histological analysis revealed increased mucosal remodeling and goblet cell hyperplasia following combined exposure. Other combinations, such as PM2.5 with formaldehyde, also induced additive or modestly enhanced inflammatory responses. Coexposure to PM2.5, formaldehyde, and zinc aggravated allergic inflammation in an OVA-induced murine model, with PM2.5 + zinc showing the strongest synergistic effects. These findings highlight the importance of pollutant-pollutant interactions in allergic airway diseases and underscore the need for further studies to elucidate longterm health impacts and human relevance.