Trune D R, Kempton J B, Mitchell C R, Hefeneider S H
Oregon Hearing Research Center, Department of Otolaryngology - Head and Neck Surgery, Oregon Health Sciences University, Portland 97201, USA.
Hear Res. 1998 Feb;116(1-2):65-70. doi: 10.1016/s0378-5955(97)00198-6.
Heat shock protein 70 (HSP70) has been suggested as the putative cochlear antigen underlying a proposed autoimmune etiology in certain cases of Meniere's disease and idiopathic hearing loss. To determine if antibodies to this cellular protein are capable of altering cochlear function, BALB/c (N= 3) and CBA/J (N= 9) mice were inoculated with bovine HSP70 by intraperitoneal injections (10 microg in saline) every 10 days for 7 or 10 months, respectively. An equal number of control mice were injected with PBS according to the same schedule. ABR thresholds at 4, 8, 16, and 32 kHz in the HSP70-inoculated mice did not change over the 10 month period and were similar to saline controls. Furthermore, serum immune complexes and antinuclear antibodies did not increase over the inoculation period. ELISA analysis demonstrated the mice created antibodies to the foreign HSP70, but these apparently caused no abnormalities in the auditory or immune systems. It was concluded that foreign HSP70 is antigenic and inoculation with it will raise antibodies, but these antibodies were neither immunopathogenic nor cochleopathic. Therefore, these findings do not support current theories that elevated anti-HSP70 antibodies are the underlying cause of hearing loss in patients with such antibodies present.
热休克蛋白70(HSP70)被认为是某些梅尼埃病和特发性听力损失病例中假定的自身免疫病因所涉及的耳蜗抗原。为了确定针对这种细胞蛋白的抗体是否能够改变耳蜗功能,分别以每10天腹腔注射(盐水中10微克)的方式,给BALB/c小鼠(N = 3)和CBA/J小鼠(N = 9)接种牛HSP70,持续7个月或10个月。按照相同的时间表给相同数量的对照小鼠注射磷酸盐缓冲液(PBS)。在10个月的时间里,接种HSP70的小鼠在4、8、16和32千赫处的听性脑干反应(ABR)阈值没有变化,并且与盐水对照组相似。此外,在接种期间血清免疫复合物和抗核抗体没有增加。酶联免疫吸附测定(ELISA)分析表明小鼠产生了针对外源HSP70的抗体,但这些抗体显然未在听觉或免疫系统中引起异常。得出的结论是,外源HSP70具有抗原性,接种它会产生抗体,但这些抗体既不具有免疫致病性也不具有耳蜗致病性。因此,这些发现不支持当前的理论,即抗HSP70抗体升高是存在此类抗体的患者听力损失的根本原因。