Get access

The role of TNF-α in inflammatory olfactory loss§

Authors

  • Babar Sultan MD,

    1. Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A
    Search for more papers by this author
  • Lindsey A. May BS,

    1. Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A
    Search for more papers by this author
  • Andrew P. Lane MD

    Corresponding author
    1. Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland, U.S.A
    • Department of Otolaryngology—Head and Neck Surgery, Johns Hopkins Outpatient Center, 601 N. Caroline Street, 6th floor, Baltimore, MD 21287-0910
    Search for more papers by this author

  • This article was supported by the National Institute of Deafness and Other Communication Disorders, National Institutes of Health Grant RO1 DC009026 (to A.P.L.).

  • The authors have no financial disclosures for this article.

  • §

    The authors have no conflicts of interest to declare.

Abstract

Background:

Despite the significant health impact of olfactory loss in chronic rhinosinusitis (CRS), the underlying pathophysiology is incompletely understood. A transgenic mouse model of olfactory inflammation induced by tumor necrosis factor-alpha (TNF-α) has provided new insights into the cellular and molecular basis of inflammatory olfactory loss. Here, we utilize systemic corticosteroids to suppress downstream cytokine expression, in order to study the direct role of TNF-α in CRS-associated olfactory dysfunction.

Methods:

Transgenic mice were induced to express TNF-α in the olfactory epithelium for 6 weeks. In a subset of mice, 1 mg/kg prednisolone was administered concurrently to inhibit downstream inflammatory responses. The olfactory epithelium (OE) was analyzed by histology and electro-olfactogram (EOG) recordings.

Results:

Treatment with prednisolone successfully prevented inflammatory infiltration over significant regions of the OE. In areas where significant subepithelial inflammation was present, a corresponding loss of olfactory neurons was observed. In contrast, areas without major inflammatory changes had normal olfactory neuron layers, despite chronic local expression of TNF-α. Prednisolone partially reversed the complete loss of olfaction in the mouse model, preserving odorant responses that were significantly diminished compared to controls, but not absent.

Conclusions:

The addition of prednisolone to the transgenic model of olfactory inflammation isolates the direct effects of induced TNF-α expression on the OE. The finding that prednisolone treatment prevents neuronal loss in some regions of the OE suggests that TNF-α does not directly cause neuronal apoptosis—rather, that subepithelial inflammation or other downstream mediators may be responsible. At the same time, EOG results imply that TNF-α directly causes physiologic dysfunction of olfactory neurons, independent of the inflammatory state. An understanding of the role of TNF-α and other inflammatory cytokines may suggest novel therapeutic strategies for CRS-associated olfactory loss.

Ancillary