title: Characterization of a novel high-dose ovalbumin-induced murine model of allergic sinonasal inflammation.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Baltimore, MD.
authors.forename: Michelle
authors.initials: M
authors.lastname: Mendiola
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Baltimore, MD.
authors.forename: Anuj
authors.initials: A
authors.lastname: Tharakan
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Baltimore, MD.
authors.forename: Mengfei
authors.initials: M
authors.lastname: Chen
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Baltimore, MD.
authors.forename: Tomefa
authors.initials: T
authors.lastname: Asempa
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Baltimore, MD.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
authors.affiliation: Division of Rhinology and Sinus Surgery, Department of Otolaryngology-Head and Neck Surgery, Baltimore, MD. mramana3@jhmi.edu.
authors.forename: Murugappan
authors.initials: M
authors.lastname: Ramanathan
mesh_terms: D000485:Allergens; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D019819:Budesonide / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D005260:Female; D006967:Hypersensitivity / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017817:Nasal Lavage Fluid / Q000276:immunology; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology; D010047:Ovalbumin; D012333:RNA, Messenger / Q000378:metabolism; D012852:Sinusitis / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000473:pathology
chemical_list: D000485:Allergens; D000893:Anti-Inflammatory Agents; D016207:Cytokines; D012333:RNA, Messenger; D019819:Budesonide; D010047:Ovalbumin
keywords: allergic rhinosinusitis; eosinophilia; mouse model; ovalbumin