title: 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 3 months of age and then treated with aldosterone (3.0 μg/kg) or prednisolone (1.0 mg/kg) to determine the lowest effective dose of each. Other mice were given the two steroids in combination at doses of Pred 0.5 mg+Aldo 1.5 μg; Pred 1.0 mg+Aldo 3.0 μg; or Pred 1.5 mg+Aldo 5.0 μg. Mice were retested with ABR at 1 and 2 months 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 (2.8 μg/kg) or high (10 μg/kg) doses and retested at monthly intervals for 3 months. Autoimmune mouse hearing loss developed in untreated controls. This threshold elevation was not prevented by prednisolone at 1 mg/kg or by aldosterone at 3 μg/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.
authors.affiliation: Oregon Hearing Research Center, Department of Otolaryngology-Head and Neck Surgery, Oregon Health & Science University, Portland, OR 97239-3098, USA. truned@ohsu.edu
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Trune
authors.forename: J Beth
authors.initials: JB
authors.lastname: Kempton
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000450:Aldosterone / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D001327:Autoimmune Diseases / Q000150:complications / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination / Q000379:methods; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005438:Fludrocortisone / Q000031:analogs & derivatives / Q000627:therapeutic use; D034381:Hearing Loss / Q000188:drug therapy* / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011239:Prednisolone / Q000627:therapeutic use; D013256:Steroids / Q000627:therapeutic use*; D013997:Time Factors
chemical_list: D013256:Steroids; D000450:Aldosterone; D011239:Prednisolone; D005438:Fludrocortisone; C034635:fludrocortisone acetate
references.citation: Hear Res. 2002 Oct;172(1-2):127-36
references.pmid: 12361875
references.citation: Otol Neurotol. 2005 Sep;26(5):908-17
references.pmid: 16151337
references.citation: Semin Arthritis Rheum. 2004 Oct;34(2):538-43
references.pmid: 15505769
references.citation: Am J Physiol Cell Physiol. 2007 Oct;293(4):C1187-208
references.pmid: 17670895
references.citation: Clin Lab Med. 1997 Sep;17(3):581-94
references.pmid: 9316775
references.citation: Clin Otolaryngol Allied Sci. 2003 Dec;28(6):479-88
references.pmid: 14616662
references.citation: Hear Res. 2007 Apr;226(1-2):209-17
references.pmid: 17098384
references.citation: J Clin Invest. 1967 Mar;46(3):429-35
references.pmid: 6023777
references.citation: J Clin Invest. 1968 Jun;47(6):1269-80
references.pmid: 4298249
references.citation: Pflugers Arch. 2006 Oct;453(1):11-22
references.pmid: 16773381
references.citation: Otolaryngol Head Neck Surg. 1997 Feb;116(2):146-52
references.pmid: 9051055
references.citation: Am J Physiol Cell Physiol. 2009 Mar;296(3):C544-57
references.pmid: 19144862
references.citation: J Neurosci. 2009 Dec 16;29(50):15851-8
references.pmid: 20016101
references.citation: Eur J Pharmacol. 1993 Oct 15;247(2):145-54
references.pmid: 8282004
references.citation: Otolaryngol Clin North Am. 2004 Oct;37(5):1061-74
references.pmid: 15474111
references.citation: Hear Res. 2005 Nov;209(1-2):10-8
references.pmid: 16039078
references.citation: Audiol Neurootol. 2002 Mar-Apr;7(2):100-6
references.pmid: 12006737
references.citation: Ear Nose Throat J. 1996 Aug;75(8):502-5, 509-10, 511-2 passim
references.pmid: 8828274
references.citation: Physiol Rev. 2006 Oct;86(4):1151-78
references.pmid: 17015487
references.citation: Acta Otolaryngol Suppl. 1997;526:30-6
references.pmid: 9107353
references.citation: Otolaryngol Clin North Am. 2004 Oct;37(5):955-72, v
references.pmid: 15474104
references.citation: Otolaryngol Head Neck Surg. 1999 Oct;121(4):452-6
references.pmid: 10504603
references.citation: Ann Otol Rhinol Laryngol. 2002 Nov;111(11):989-97
references.pmid: 12450172
references.citation: Otolaryngol Head Neck Surg. 1997 Nov;117(5):504-8
references.pmid: 9374175
references.citation: Otolaryngol Head Neck Surg. 1995 Jun;112(6):639-53
references.pmid: 7777346
references.citation: Am J Physiol Renal Physiol. 2004 Jun;286(6):F1127-35
references.pmid: 14996671
references.citation: Hear Res. 2001 May;155(1-2):9-20
references.pmid: 11335072
references.citation: Otolaryngol Head Neck Surg. 2006 May;134(5):783-7
references.pmid: 16647535
references.citation: Arch Otolaryngol Head Neck Surg. 2001 Mar;127(3):253-8
references.pmid: 11255468
references.citation: Am J Physiol Cell Physiol. 2008 Jul;295(1):C73-80
references.pmid: 18463232
references.citation: Annu Rev Med. 1997;48:231-40
references.pmid: 9046958
references.citation: Audiol Neurootol. 2009;14(6):423-31
references.pmid: 19923812
references.citation: Autoimmunity. 2006 Mar;39(2):153-8
references.pmid: 16698672
references.citation: Otolaryngol Head Neck Surg. 1997 Nov;117(5):530-4
references.pmid: 9374179
references.citation: Audiol Neurootol. 1999 Mar-Apr;4(2):80-7
references.pmid: 9892758
references.citation: Hear Res. 2006 Feb;212(1-2):22-32
references.pmid: 16307853