Age-related cochlear cytokine gene expression in the BALB/cJ mouse with systemic versus intratympanic dosing of steroid drugs

Abstract

Conclusion: Age-related differences in the expression of inflammatory cytokines in the inner ear may contribute to the development of age-related hearing loss (ARHL). Objectives: ARHL is characterized by tissue remodeling, ischemia, ion homeostasis, and inflammation. Steroid therapy is an otoprotective strategy that likely acts by reducing inflammation. We examined age-related changes in cytokine gene expression in the cochlea of the BALB/cJ mouse model of premature ARHL after systemic or intratympanic steroid delivery. Methods: ‘Young' (2.5–3 months) and ‘Old' (5–9 months) mice were treated with dexamethasone or fludrocortisone administered either orally or intratympanically. Cytokine gene expression in cochlear RNA was analyzed using prefabricated cDNA arrays. Old groups were compared to Young groups to identify age-related changes. Results: Down-regulation of a cytokine associated with bone remodeling (SPP1) was observed in the untreated Old group. Numerous genes were up- or down-regulated by more than twofold by steroid treatment, including proinflammatory interleukins (IL-16) and anti-inflammatory cytokines.

Keywords::

• Aging
• animal model
• glucocorticoid
• inflammation
• inner ear
• mineralocorticoid
• sensorineural hearing loss
• SPP1

Acknowledgments

We thank Jens Eickhoff PhD, University of Wisconsin-Madison Department of Biostatistics & Medical Informatics, for helpful review of the statistics applied in this manuscript. This work was funded through NIH grant NIH-NIDCD R01 DC05593 (D.R.T.), the Doernbecher Foundation (D.M.P.), the OHSU Department of Pediatrics (D.M.P.), and the University of Wisconsin-Madison Department of Pediatrics (D.M.P.).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.