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

Abstract

Objectives: Allergic rhinitis (AR) is a chronic inflammation of the nasal mucosa triggered by environmental allergens. Although its pathophysiology has been extensively investigated, the influence of environmental aggravating factors-particularly combined pollutant exposure-remains insufficiently characterized. This study aimed to assess the impact of coexposure to PM2.5, formaldehyde, and Zn on allergic inflammation in a murine AR model and to delineate the associated immunological and histopathological responses.

Methods: Female BALB/c mice were sensitized with ovalbumin (OVA) and challenged intranasally to induce AR. On days 21-24, the mice were exposed to PM2.5, formaldehyde, and Zn, either individually or in combination with OVA. Allergic symptoms were evaluated through behavioral observation, while immune responses were assessed by analyzing nasal and bronchoalveolar lavage fluids (NALF and BALF), serum immunoglobulin levels, nasal histopathology, and cytokine profiles.

Results: Combined exposure to PM2.5, formaldehyde, and Zn significantly intensified allergic inflammation compared with single exposures. Coexposure to PM2.5 and Zn led to synergistic increases in total and OVA-specific immunoglobulin E levels, eosinophilic infiltration, nasal rubbing, sneezing, and Th2/Th17 cytokine levels in NALF and BALF. Histological analysis demonstrated epithelial thickening and goblet cell hyperplasia after combined exposure. Other combinations, including PM2.5 with formaldehyde, also produced additive or modestly amplified inflammatory responses.

Conclusion: Coexposure to PM2.5, formaldehyde, and Zn aggravated allergic inflammation in an OVA-induced murine model, with PM2.5+Zn yielding the strongest synergistic effects. These findings emphasize the role of pollutant-pollutant interactions in allergic airway diseases and highlight the need for further research to clarify long-term health effects and relevance to human disease.