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The role of cytokines in varal infection and in allergy in the respiratory tract was evaluated.

评估了细胞因子在呼吸道感染和过敏中的作用。

基本信息

批准号：
09470369
负责人：
OKAMOTO Yoshitaka
金额：
$ 8.38万
依托单位：
Yamanashi Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1999
项目状态：
已结题

项目摘要

(1) The characteristics of the cytokines and immunity induced by viral antigen via different administration routes was comparatively evaluated. C57BL/6 mice were immunized via intranasal, intradermal, or enteric routes with a live recombinant vaccinia virus expressing the respiratory syncytial virus(RSV) G glycoprotein(r. Gvv) or F glycoprotein(r. FVV) and challenged intranasally with RSV Th2 cytokines were dominantly detected in the bronchoalveolar lavage of the mice immunized with r. GVV intradermally, and Th1 cytokines were dominant of the mice immunized with r. FVV intradermally, although their concentration was lower in the enteric and intranasal immunization groups. Resistance to RSV replication was observed in the lung of all groups of mice, however, in the nose only of intranasal immunization group. Lung inflammation characterized by infiltration of mononuclear cells and of eosinophils was strongest in the G.rVV intradermal immunization group, although observed in all groups to various degrees.(2) The role of IL-10 in nasal allergy and RSV infection was evaluated with transgenic mice which showed high expression of IL- 10 protein in nasal mucosa as well as in salivary glands.After intranasal administration with RSV, viral replication in respiratory tract of the transgenic mice was significantly suppressed compared with that control non-transgenic mice. The suppression of viral replication was not observed in anti-IL-10 treated transgenic mice and Fas/Fas L system mediated CTL may be involved in the suppression of RSV replication observed in IL-10 transgenic mice.In additional study, the transgenic mice were sensitized with ovalbumin. Nasal symptoms were stronger and Th2 cytokines production in nasopharyngeal lymphoid tissue and the number of eosinophils in nasal mucosa were found to be significantly higher in transgenic mice compared with those in control mice. IL-10 may affect on the development of the dysregulation of Th1/Th2 cytokines.

(1)比较分析了不同给药途径对病毒抗原诱导的细胞因子和免疫反应的影响。通过鼻内、皮内或肠道途径用表达呼吸道合胞病毒（RSV）G糖蛋白的活重组牛痘病毒（r.r. Gvv）或F糖蛋白（r. FVV）和RSV Th 2细胞因子鼻内攻击的小鼠的支气管肺泡灌洗液中主要检测到r.皮内接种GVV，以Th 1型细胞因子为主。FVV皮内，虽然他们的浓度较低的肠道和鼻内免疫组。在所有组小鼠的肺中观察到对RSV复制的抵抗，然而，鼻内免疫组仅在鼻中观察到对RSV复制的抵抗。以单核细胞和嗜酸性粒细胞浸润为特征的肺部炎症在G.rVV皮内免疫组中最强，尽管在所有组中都观察到不同程度的炎症。(2)用鼻粘膜和唾液腺中均高表达IL-10蛋白的转基因小鼠研究了IL-10在鼻变态反应和RSV感染中的作用，结果表明，经鼻内给予RSV后，转基因小鼠呼吸道中的病毒复制比非转基因小鼠明显受到抑制。抗IL-10处理的转基因小鼠未观察到病毒复制的抑制，Fas/Fas L系统介导的CTL可能参与了IL-10转基因小鼠RSV复制的抑制。与对照组小鼠相比，转基因小鼠鼻症状明显加重，鼻咽部淋巴组织中Th 2细胞因子的产生和鼻粘膜中嗜酸性粒细胞的数量明显增多。IL-10可能影响Th 1/Th 2细胞因子失调的发展。