全世界過敏性氣喘的盛行率有逐年增加的趨勢。對於過敏原的接觸誘使人體致敏，造成過敏性疾病發生，進而再接觸到致敏的過敏原後，會引起嚴重局部性的肺部發炎反應。這當中的致病機制還沒完全釐清。此外，連續低劑量的給予過敏原已經被證實可以誘使免疫系統產生免疫耐受性，進而對抗過敏原誘發的呼吸道發炎反應。在本實驗當中，我們假設不同的免疫原（如：脂多醣和家塵螨過敏原）可以導致不同的肺部抗原呈現細胞（如：肺部樹突狀細胞）比例，進而產生功能上的轉變，造成後續免疫反應的不同。透過小鼠致敏前預先給予連續低劑量的脂多醣或塵螨蛋白質萃取物也許能影響肺部樹突狀細胞去改變過敏原誘發的氣喘性發炎症狀。因此實驗小鼠分別在致敏前以單次高劑量或連續低劑量的方式，在氣管內注射生理食鹽水、塵螨蛋白質萃取物或脂多醣。實驗結果與給予生理食鹽水的塵螨致敏小鼠相比，預先連續低劑量給予塵螨蛋白質萃取物可以使塵螨致敏小鼠的血清中塵螨專一性免疫球蛋白質E表現顯著下降，並且在肺部沖洗液中細胞總數及嗜酸性球的數量上也有顯著性的下降。連續性的給予塵螨蛋白質萃取物或脂多醣也可以造成塵螨致敏小鼠的呼吸道過度性反應以及肺部病理切片上的發炎情形下降。這些結果顯示，預先給予連續低劑量塵螨蛋白質萃取物可以使小鼠達到較好的免疫耐受性，而預先給予脂多醣則無法產生較好的耐受性。在預先給予塵螨蛋白質萃取物的小鼠肺部組織中發現有較高比例的plasmacytoid DCs，而myeloid DCs則是在縱膈腔淋巴結中有較高的比例存在。另外，由塵螨致敏小鼠收集的肺部沖洗液中發現，細胞激素（IL-4、IL-13、IL-10和IFN-γ）分泌量沒有顯著性的變化。然而經過預先給予連續低劑量塵螨蛋白質萃取物，在小鼠肺部組織中的樹突狀細胞表面主要組織相容性複合體表現量比控制組的比例要低。綜合所有結果，預先連續低劑量給予塵螨蛋白質萃取物或脂多醣可以降低過敏原誘發的氣喘性發炎反應，這個機制可能由於樹突狀細胞的成熟活化以及分佈造成影響，而非預期的細胞比例上的不同所造成。

The prevalence of allergic asthma is increasing yearly in all over the world. Exposure to aeroallergens induces sensitization of host and serious local inflammation in the lung after recurrent contacts of sensitized allergens, but the mechanism by which allergen-induced asthmatic inflammation is still unclear. In contrast, repeated low dose allergens administrations were reported to induce immune tolerance against allergen-induced airway inflammation. We hypothesized that different airborne immunogens, such as lipopolysaccharide (LPS) and house dust mite allergen (Der p extracts) act on local antigen presenting cells, such as dendritic cells in the lung (lung DCs), to induce different types of local immune response by the changes of populations and functions. Repeated low dose administrations of Der p extracts (DP) or LPS before allergen sensitization in mice may influence lung DCs to ameliorate the severity of allergen-induced asthmatic inflammation. Therefore, DP-sensitized mice were intra-tracheally pre-treated with normal saline (NS), DP, and LPS, respectively, in single or repeated low doses administrations before allergen sensitization. As compared to NS administrations, repeated low dose administrations of DP decreased DP-specific IgE in serum and total cells numbers and eosinophils infiltration in bronchoalveolar lavage fluids (BALF) in allergen- challenged sensitized mice. Airway hyperresponsiveness (AHR) and inflammation in pathology also reduced in sensitized mice with repeated low dose administrations of DP or LPS. These results show that repeated DP administration before sensitization induced well-immunotolerance, not LPS. Administration of DP before allergen sensitization demonstrated higher percentage of plasmacytoid DCs (pDCs) in lung and higher percentage of myeloid DCs (mDCs) in the mediastrial draining lymph nodes (MLN). There was no significant difference of secreted cytokines (IL-4, IL-13, IL-10, and IFN-γ) in BALF between DP and NS (controlled) pre-treated allergen sensitized mice. However, the expression levels of major histocompatibility complex (MHC) class II in lung DCs were decreased in sensitized mice with repeated DP administrations as compared with controlled sensitized mice. In summary, repeated low dose administrations of DP or LPS can reduce allergen-induced asthmatic inflammation. This mechanism may due to the effect on DCs maturation and localization, instead of the percentage change of pDCs and mDCs population.

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