Inhibition of inflammation-associated olfactory loss by etanercept in an inducible olfactory inflammation mouse model

Yong Gi Jung, Andrew P. Lane

Research output: Contribution to journalArticlepeer-review

Abstract

Objective 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. Study Design An in vivo study using a transgenic mouse model. Setting Research laboratory. Subjects and Methods 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. Results 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. Conclusion 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.

Original languageEnglish (US)
Pages (from-to)1149-1154
Number of pages6
JournalOtolaryngology - Head and Neck Surgery (United States)
Volume154
Issue number6
DOIs
StatePublished - Jun 1 2016

Keywords

  • TNF-α
  • inflammation
  • olfactory loss
  • rhinosinusitis
  • transgenic model

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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