Inhibition of Inflammation-Associated Olfactory Loss by Etanercept in an Inducible Olfactory Inflammation Mouse Model

Objective To determine the effect of a soluble human tumor necrosis factor alpha (TNF-) 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- in a temporally controlled fashion within the olfactory epithelium. In one group of mice (n = 4), etanercept was injected intraperitoneally (100 g/dose, 3 times/week) concurrent with a 2-week period of TNF- expression. A second group of mice (n = 2) underwent induction of TNF- 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--induced olfactory loss and induction of neuroepithelial regeneration. This demonstrates that etanercept has potential utility as a tool for elucidating the role of TNF- in other olfactory inflammation models.