Low dose combination steroids control autoimmune mouse hearing loss

Abstract 

The severe side effects of glucocorticoids prevent long term management of hearing loss. Alternative steroid treatments that minimize or eliminate these effects would significantly benefit therapeutic control of hearing disorders. A steroid treatment study of autoimmune mouse hearing loss was conducted to determine the efficacy of combining aldosterone and prednisolone at low doses. An assessment also was made of low dose fludrocortisone, a synthetic mineralocorticoid that also has a slight glucocorticoid effect. MRL/MpJ-Fas^lpr mice were tested for baseline ABR thresholds at 3months of age and then treated with aldosterone (3.0μg/kg) or prednisolone (1.0mg/kg) to determine the lowest effective dose of each. Other mice were given the two steroids in combination at doses of Pred 0.5mg+Aldo 1.5μg; Pred 1.0mg+Aldo 3.0μg; or Pred 1.5mg+Aldo 5.0μg. Mice were retested with ABR at 1 and 2months to determine the efficacy of the different steroid treatments in controlling hearing loss. Another series of mice were given the synthetic mineralocorticoid fludrocortisone at low (2.8μg/kg) or high (10μg/kg) doses and retested at monthly intervals for 3months. Autoimmune mouse hearing loss developed in untreated controls. This threshold elevation was not prevented by prednisolone at 1mg/kg or by aldosterone at 3μg/kg when each was given alone. However, the two steroids combined at these doses effectively controlled hearing loss. The fludrocortisone treatments also were effective at low doses in preventing or reversing the autoimmune mouse hearing loss. This efficacy of combined steroids at low doses suggests the potential for reducing the side effects of glucocorticoids in the therapeutic control of hearing disorders.

Keywords: Autoimmune hearing loss, Inner ear, MRL/MpJ-Fas^lpr autoimmune mice, Prednisolone, Aldosterone, Fludrocortisone, Adrenocorticosteroids