title: Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model.
abstract: To determine the effect of a soluble human tumor necrosis factor alpha (TNF-α) receptor blocker (etanercept) on an inducible olfactory inflammation (IOI) mouse model.
  
  
  
  An in vivo study using a transgenic mouse model.
  
  
  
  Research laboratory.
  
  
  
  To study the impact of chronic inflammation on the olfactory system, a transgenic mouse model of chronic rhinosinusitis-associated olfactory loss was utilized (IOI mouse), expressing TNF-α in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 μg/dose, 3 times/week) concurrent with a 2-week period of TNF-α expression. A second group of mice (n = 2) underwent induction of TNF-α expression for 8 weeks, with etanercept treatment administered during the final 2 weeks of inflammation. Olfactory function was assayed by elecro-olfactogram (EOG), and olfactory tissue was processed for histology and immunohistochemical staining. Each group was compared with an equal-number control group.
  
  
  
  Compared with nontreated IOI mice, etanercept-treated IOI mice showed significantly improved EOG responses after 2 weeks (P < .001). After 8 weeks of induced inflammation, there was massive loss of olfactory epithelium and no EOG response in nontreated IOI mice. However, in etanercept-treated mice, regeneration of olfactory epithelium was observed.
  
  
  
  Concomitant administration of etanercept in IOI mice results in interruption of TNF-α-induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF-α in other olfactory inflammation models.
authors.affiliation: Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon-Si, Korea ent.jyg@gmail.com.
authors.forename: Yong Gi
authors.initials: YG
authors.lastname: Jung
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Lane
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000068800:Etanercept / Q000494:pharmacology*; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications; D051379:Mice; D008822:Mice, Transgenic; D000857:Olfaction Disorders / Q000188:drug therapy* / Q000209:etiology; D012220:Rhinitis / Q000150:complications; D012852:Sinusitis / Q000150:complications
chemical_list: D000068800:Etanercept
keywords: TNF-α; inflammation; olfactory loss; rhinosinusitis; transgenic model