- 學位論文
探討zymosan在小鼠氣喘動物模式上的治療效果
The therapeutic effects of zymosan on OVA-induced asthmatic mice
摘要
最近許多研究發現，多種不同的類鐸受體興奮劑在人體試驗上證實可以有加強減敏治療的效果，而由近期的臨床資料顯示，其可能是透過誘發對過敏原有專一性的Th1免疫反應來達到加強減敏治療的效果，但目前還尚未探討zymosan是否可以使用在減敏治療上，因此本研究想透過氣喘發病的動物平台來評估zymosan是否有能力在體內引起過敏原專一性的Th1免疫反應來抑制過敏原專一性Th2免疫反應的產生。在動物實驗中，經由腹腔或皮下注射ovalbiumin(OVA)/鋁佐劑途徑合併不同濃度的zymosan(10、50及100 ?慊)使用下，結果發現有zymosan治療組別血液中OVA專一性IgG2a含量增加，並降低OVA專一性IgE及IgG1的生成。另外，zymosan可以引起肺部的Th1免疫反應並有效抑制嗜酸性白血球聚集以及Th2免疫反應的發生，改善氣管過度收縮反應及肺部發炎現象。至於評估透過鼻腔單獨注射zymosan來治療氣喘小鼠的模式中則可以觀察到，可以有效抑制肺部的Th2免疫反應，但效果沒有前兩種模式好。在本研究中也發現，zymosan會引起Th17免疫反應雖有助於改善過敏氣喘症狀，但會造成嗜中性白血球聚集的現象。綜合以上結果，我們認為zymosan確實具有調節免疫的功能，而在減敏治療中加入zymosan做為佐劑可以誘導過敏原專一性Th1與Th17免疫反應，以提升減敏治療的效果，但在將來應用到人體實驗上還需要更深入的探討。
關鍵字
氣喘並列摘要
Currently, the different toll-like receptor agonists are tested in humans for their ability to enhance the efficacy of allergen specific immunotherapy (ASIT). The clinical data imply that this may be achieved by increasing allergen-specific Th1 responses. However, it’s not clear whether zymosan can be used in ASIT. In our study, we want to evaluate whether administration of zymosan can induce allergen-specific Th1 response to suppress allergen-specific Th2 response in vivo. In ovalbiumin (OVA)-induced asthmatic model, Balb/c mice were immunized with OVA and aluminum hydroxide in the presence of zymosan by intraperitoneal or subcutaneous routes. We observed that zymosan efficiently enhanced increase OVA-specific IgG2a production, and reduced expression levels of OVA-specific IgE and IgG1. Further, the administration of zymosan inhibited the development of airway hyperresponsiveness, airway eosinophilia and Th2 response. We also found that zymosan induced Th17 response; therefore, IL-17 attracted the infiltration of neutrophils in the lungs. Those data indicated that zymosan exhibits immune-modulatory properties and suggest that such effect may be associated to the induction of Th1 and Th17 response. Similarly, mice were treated intranasally with zymosan. It also showed that zymosan alleviated the development of asthma. Taken together, our data suggest that zymosan may be used as an adjuvant to enhance the efficacy of ASIT. However, if zymosan is used to apply in clinical trial, it still need more research to understand the side effect of zymosan.