Aldosterone and prednisolone control of cochlear function in MRL/MpJ-Fas(lpr) autoimmune mice.
Recently this laboratory showed aldosterone, a mineralocorticoid that only enhances sodium transport, was as effective as the glucocorticoid prednisolone in restoring cochlear function in autoimmune mice. To further test this relationship between sodium transport and autoimmune hearing loss, dosage comparisons were made of prednisolone and aldosterone control of the auditory dysfunction in autoimmune MRL/MpJ-Fas(lpr) mice. Mice were tested at 2 months of age to establish baseline auditory brainstem response (ABR) thresholds, hematocrit, serum immune complexes, and anti-nuclear antibodies. Mice were then given different doses of prednisolone or aldosterone in their drinking water for 2 months. After the treatment period, most untreated water controls showed elevation of ABR thresholds due to the ongoing autoimmune disease. However, the steroid groups had significantly more mice with improved or unchanged thresholds. Both steroids improved stria vascularis morphology, although aldosterone appeared to be more effective. The immune suppressive prednisolone caused a dose-related improvement in levels of serum immune complexes and hematocrit, hallmarks of systemic autoimmune disease. Aldosterone, which has no immune suppressive function, did not alter systemic disease. The comparable efficacy of prednisolone and aldosterone in restoring auditory function suggests steroid reversal of autoimmune hearing loss in mice is due to increasing stria vascularis sodium transport and not suppression of systemic autoimmune reactions.
Trune
D R
DR
Oregon Hearing Research Center, Mail Code NRC04, Department of Otolaryngology, Head and Neck Surgery, Oregon Health Sciences University, 3181 SW Sam Jackson Park Road, 97201-3098, Portland, OR, USA. truned@ohsu.edu
Kempton
J B
JB
D000450:Aldosterone / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D003051:Cochlea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003638:Deafness / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D051379:Mice; D019463:Mice, Inbred MRL lpr; D011239:Prednisolone / Q000008:administration & dosage / Q000494:pharmacology*
D000450:Aldosterone; D011239:Prednisolone