Eosinophil Cationic Protein (ECP) intranasal administration induces type 2 olfactory dysfunction in mice

Eosinophilic chronic rhinosinusitis (ECRS) is a debilitating inflammatory condition marked by significant eosinophil infiltration and frequently associated with olfactory dysfunction (OD). Despite its prevalence, the precise mechanisms linking eosinophil-driven inflammation to OD remain poorly understood. Current treatments often fall short in addressing the underlying causes of OD in ECRS. This study addresses this gap by developing a rapid, reproducible murine model to investigate how eosinophil products contribute to olfactory impairment, specifically focusing on type 2 inflammation pathways.

To establish a murine model of eosinophil-induced OD (EIOD), male mice received intranasal administration of Eosinophil Cationic Protein (ECP) for durations of 10 and 20 days. The efficacy and validity of this model were rigorously assessed through a comprehensive suite of experiments. These included behavioral assessments to quantify olfactory function, detailed histological examinations of the olfactory epithelium, cytokine analysis of nasal lavage fluid using ELISA or similar methods, and gene expression profiling via RNA sequencing to identify altered molecular pathways. Control groups were implicitly compared against baseline or untreated animals.

Behavioral assessments conclusively demonstrated the presence of olfactory dysfunction in ECP-treated mice. Histological analysis revealed a significant thinning of the olfactory epithelial mucosa, coupled with a marked reduction in the number of olfactory sensory neurons. Concurrently, an increase in key type 2 inflammatory cytokines (e.g., IL-4, IL-5, IL-13) was detected in the nasal lavage fluid, confirming the inflammatory response. Notably, upon cessation of ECP administration, both olfactory function and the structural integrity of the olfactory mucosa exhibited clear signs of recovery. Furthermore, RNA sequencing analysis provided deeper insights, revealing specific alterations in certain inflammatory immune pathways, underscoring the molecular basis of the observed dysfunction. This study effectively established a robust model for EIOD.

The model demonstrated that ECP-induced olfactory dysfunction and epithelial damage were reversible upon cessation of ECP administration, highlighting the dynamic nature of type 2 inflammatory impact.