The present study further assessed the role of the endolymphatic sac (E.S.) in the generation of inner ear immune responses. Guinea pigs underwent unilateral endolymphatic sac obliteration (Rt) and the opposite ears (Lt) served as controls. The animals were then systemi-cally sensitized to KLII and both inner ears were subsequently challenged with KLU. Absence of the E.S. significantly reduced perilymph anti-KLH levels and greatly reduced cellular infiltration within the cochlea as compared to the control ears (Lt). Control studies demonstrated that neither surgical trauma to the semicircular canal nor the chemical effects of silver nitrate caused immunosuppression of the normal inner ear immune response. From these findings, the E.S. appears to be the main site of antigen processing in the inner ear and a site analogous to the gut with respect to absorptive and immunologic functions.
The present study investigated immune injury associated with endolymphatic hydrops (e.hydrops) following locally mounted immune reaction in the endolymphatic sac (e.sac) of guinea pigs. E.hydrops occurred, progressing rapidly within the first week post secondary Keyhole limpet hemocyanin (KLH) challenge in the e.sac and developed into two phases, acute and chronic. On the other hand, primary KLH challenge of the e.sac, PBS inoculation into the e.sac or intradural secondary KLH challenge were incapable of inducing e.hydrops. These results indicate that reversible and irreversible e.hydrops are induced by the immune response of the e.sac, suggesting that local immunological events of the e.sac may provide an animal model of Meniere's disease.
Recently, the efficacy of macrolide antibiotics in cystic fibrosis and bleomycin-induced lung injury was reported. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by structural abnormalities including stromal fibrosis. Fibroblasts are resident cells thought to play an important role in the development of fibrosis. Although the effect of Roxithromycin (RXM) on inflammatory cells is well known, there is no evidence on the effect of RXM on fibroblasts. The purpose of the present study was two-fold: to examine the effect of RXM on the growth of fibroblasts in vitro and to examine the effect of RXM on the proliferation of fibroblasts in vivo. Nasal polyp fibroblast lines were generated from untreated patients, and those who were treated with RXM (300 mg/day) for one month before biopsy. Nasal polyp fibroblast lines from untreated patients were cultured for 72 hours with or without RXM, and the direct effect of RXM on fibroblast growth in vitro was examined by cell counting and 3H thymidine uptake. Next, we examined the in vivo effect of RXM on nasal polyp fibroblasts (NPFs) by comparing the growth characteristics of NPF lines from RXM treated and untreated patients. Finally, we examined the proliferating rate of NPF lines from the same patient before and after treatment with RXM. NPF lines that were treated with RXM exhibited a lower proliferating rate in vitro as compared to those that were not treated with RXM. Treatment of NPF lines with RXM suppressed the proliferation of fibroblasts in a dose-dependent manner. In addition, NPF lines from patients treated with RXM exhibited a lower proliferating rate in vitro as compared to NPF lines from the same patient taken before RXM treatment. We demonstrated that RXM directly suppressed nasal polyp fibroblast proliferation, and that this effect of RXM on fibroblast growth was persistent, indicating that RXM may prevent the progression of nasal polyposis by inhibiting the development of fibrosis.
The effect of direct antigen challenge of the endolymphatic sac (e.sac) on inner ear antibody levels was investigated in guinea pigs. Two weeks following e.sac antigen inoculation, perilymph antibody levels to keyhole limpet hemocyanin (KLH) were found to be significantly elevated in the challenged ear of those animals compared to the unchallenged, opposite ear. Moreover, when the endolymphatic duct (e.duct) in a group of animals were obstructed prior to antigen challenge of their e.sac then the rise in perilymph antibody was prevented. The local accumulation of plasma cells and lymphocytes in the perisaccular space and e.sac lumen was seen following these antigen injections. These experiments suggest that inner ear antibody emanates from the e.sac and reaches the perilymphatic compartment along the route of the e.duct. Furthermore, these findings emphasize the central role of the e.sac in inner ear immunity.
This study investigated the effect of a secondary immune response in the endolymphatic sac on the development of endolymphatic hydrops in guinea pigs. Following secondary keyhole limpet hemocyanin (KLH) challenge directly to the sac in systemically presensitized animals, hydrops rapidly developed within 1 week, then gradually reduced by 4 weeks. After 5 weeks, hydrops gradually recurred and developed again. Mean perilymph anti-KLH antibody levels rose from day 1 to 4 weeks and then decreased. The elevation of perilymph anti-KLH antibody levels on day 2 was due to an increased vascular permeability and there was a local regeneration by the challenge of the sac after day 7. The development of hydrops correlated well with mean perilymph anti-KLH antibody levels in the period from day 1 to day 7. After 2 weeks, there was no correlation between them. These results suggest that an immune response of the sac may induce an excess secretion of endolymph in the initial stage and may further lead to irreversible dysfunction of the sac at a later stage.
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