BACKGROUND: Few efficacious topical therapies exist for chronic rhinosinusitis (CRS). The lack of a reproducible mouse model of CRS limits the pilot testing of potential novel anti-inflammatory therapies. Although the ovalbumin-induced mouse model of sinonasal inflammation is commonly used, it is difficult to reproduce and can generate variable histologic results. In this study, we explore a variation of this model in different strains of mice and explore various inflammatory cytokines as reproducible molecular markers of inflammation. METHODS: Allergic sinonasal inflammation was generated in BALB/c and C57BL/6 mice using intraperitoneal high-dose injections of ovalbumin (Ova; Sigma Chemical Co.) followed by 10 days of high-dose intranasal sensitization. Real-time polymerase chain reaction (RT-PCR) for eotaxin, interleukin 4 (IL-4), and IL-13 were measured from sinonasal mucosa. We also pilot tested a known topical budesonide to characterize the anti-inflammatory response. Histological sections were analyzed for epithelial thickness and eosinophilia. RESULTS: Both BALB/c and C57BL/6 mice consistently showed increases in T helper 2 (Th2) cytokines after sensitization with high-dose Ova (p < 0.0001) when compared to controls. There were also significant increases in epithelial thickening in Ova-sensitized mice and eosinophilia in both BALB/c and C57BL/6 strains. In addition, topical budesonide significantly reduced anti-inflammatory cytokines, eosinophilia, and epithelial thickness. CONCLUSION: Our variation of the ovalbumin-induced mouse model of sinonasal inflammation in both BALB/c and C57BL/6 mice provides an efficacious model for testing potential topical anti-inflammatory therapies for CRS. The utilization of sinonasal mucosal Th2 cytokines along with histologic markers provides a consistent and quantifiable marker of inflammation in assessing the efficacy of candidate drugs.
BACKGROUND: Few efficacious topical therapies exist for chronic rhinosinusitis (CRS). The lack of a reproducible mouse model of CRS limits the pilot testing of potential novel anti-inflammatory therapies. Although the ovalbumin-induced mouse model of sinonasal inflammation is commonly used, it is difficult to reproduce and can generate variable histologic results. In this study, we explore a variation of this model in different strains of mice and explore various inflammatory cytokines as reproducible molecular markers of inflammation. METHODS:Allergic sinonasal inflammation was generated in BALB/c and C57BL/6 mice using intraperitoneal high-dose injections of ovalbumin (Ova; Sigma Chemical Co.) followed by 10 days of high-dose intranasal sensitization. Real-time polymerase chain reaction (RT-PCR) for eotaxin, interleukin 4 (IL-4), and IL-13 were measured from sinonasal mucosa. We also pilot tested a known topical budesonide to characterize the anti-inflammatory response. Histological sections were analyzed for epithelial thickness and eosinophilia. RESULTS: Both BALB/c and C57BL/6 mice consistently showed increases in T helper 2 (Th2) cytokines after sensitization with high-dose Ova (p < 0.0001) when compared to controls. There were also significant increases in epithelial thickening in Ova-sensitized mice and eosinophilia in both BALB/c and C57BL/6 strains. In addition, topical budesonide significantly reduced anti-inflammatory cytokines, eosinophilia, and epithelial thickness. CONCLUSION: Our variation of the ovalbumin-induced mouse model of sinonasal inflammation in both BALB/c and C57BL/6 mice provides an efficacious model for testing potential topical anti-inflammatory therapies for CRS. The utilization of sinonasal mucosal Th2 cytokines along with histologic markers provides a consistent and quantifiable marker of inflammation in assessing the efficacy of candidate drugs.
Authors: Michael S Benninger; Berrylin J Ferguson; James A Hadley; Daniel L Hamilos; Michael Jacobs; David W Kennedy; Donald C Lanza; Bradley F Marple; J David Osguthorpe; James A Stankiewicz; Jack Anon; James Denneny; Ivor Emanuel; Howard Levine Journal: Otolaryngol Head Neck Surg Date: 2003-09 Impact factor: 3.497
Authors: John F Alcorn; Karina Ckless; Amy L Brown; Amy S Guala; Jay K Kolls; Matthew E Poynter; Charles G Irvin; Albert van der Vliet; Yvonne M W Janssen-Heininger Journal: Am J Physiol Lung Cell Mol Physiol Date: 2009-11-06 Impact factor: 5.464
Authors: Anuj Tharakan; Alex Dobzanski; Nyall R London; Syed M Khalil; Nitya Surya; Andrew P Lane; Murugappan Ramanathan Journal: Int Forum Allergy Rhinol Date: 2018-01-17 Impact factor: 3.858