TY - JOUR
T1 - Aldosterone and prednisolone control of cochlear function in MRL/MpJ-Faslpr autoimmune mice
AU - Trune, Dennis R.
AU - Kempton, J. Beth
N1 - Funding Information:
Research supported by NIH-NIDCD R01 DC03573, NIH-NIDCD R21 DC03955, and VA RR&D National Center for Rehabilitative Auditory Research RCTR 597-0160, Portland VAMC.
PY - 2001
Y1 - 2001
N2 - 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-Faslpr 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.
AB - 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-Faslpr 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.
KW - Aldosterone
KW - Autoimmune hearing loss
KW - MRL/MpJ-Fas autoimmune mouse
KW - Prednisolone
KW - Systemic lupus erythematosus
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U2 - 10.1016/S0378-5955(01)00240-4
DO - 10.1016/S0378-5955(01)00240-4
M3 - Article
C2 - 11335072
AN - SCOPUS:0035032762
SN - 0378-5955
VL - 155
SP - 9
EP - 20
JO - Hearing Research
JF - Hearing Research
IS - 1-2
ER -