過去幾十年來，已開發國家中兒童過敏性疾病及氣喘的罹病率大幅的增加。根據hygiene hypothesis所提出的想法，認為在已開發國家，因為衛生環境和生活居住情況的改善、抗生素的使用以及家庭規模較小等因素，以致於在幼兒時期暴露於有微生物的環境減少而增加罹患過敏性疾病的機會。在臨床研究已經證實使用Lactobacillus paracasei 33 (LP33)優酪乳可以改善患有過敏性鼻炎病童的症狀，但詳細機轉並不清楚。首先，我們利用小鼠巨噬細胞株RAW 264.7及樹突細胞株DC2.4，針對LP33的刺激對於細胞激素生成的影響進行研究。結果顯示，LP33可以刺激巨噬細胞株RAW 264.7產生IL-12、IL-10、TGF-β以及誘使樹突細胞株DC2.4 IL-10 mRNA的表現，這些現象並具有劑量依存性。進一步我們想利用塵蟎過敏原致敏的小鼠模式來評估餵食含有LP33益生菌的優酪乳是否能改善塵蟎過敏原誘發的過敏性呼吸道發炎反應。BALB/c小鼠分別以餵食管餵食3x106 CFU/700 μl和9x106 CFU/700 μl兩種劑量的LP33優酪乳，自塵蟎過敏原(Dermatophoides pteronyssinus, Der p)致敏前兩星期直至以氣管內給予塵蟎過敏原作過敏性氣喘誘發當天止。我們發現給予9x106 CFU劑量的小鼠，呼吸道高度反應性及浸潤到呼吸道中的總白血球、單核白血球和淋巴球都有顯著的降低。經由肺部組織切片可以發現浸潤到氣管周圍的發炎細胞減少且呼吸道上皮細胞完整沒有損傷。此外，在肺泡沖洗液中Th1細胞激素IL-12的產量、血清中塵蟎特異性抗體IgG2a以及脾臟細胞經由Der p過敏原作特異性刺激後IFN-γ的產生都有明顯的增加。另外，在餵食3x106 CFU劑量的小鼠，我們只觀察到脾臟細胞經由Der p過敏原作特異性刺激後，IFN-γ的產生提高與脾臟細胞對Der p過敏原的刺激反應減低。綜合以上結果我們可以發現，餵食Lactobacillus paracasei 33優酪乳能藉由增進Th1免疫反應減輕過敏性呼吸道發炎反應。

The prevalence of childhood allergy and asthma has increased during the past few decades in the developed world. The hygiene hypothesis suggests that the increase in the prevalence of allergic disease is related to reduced exposure to microbes at an early age as a result of improved hygiene and living conditions, vaccines, antibiotics therapy and smaller family sizes. Clinical trails have demonstrated that earlier introduction and continuous ingestion of Lactobacillus paracasei 33 (LP33) yogurts can improve the symptoms of allergic rhinitis but the mechanisms responsible for these benefits remain unclear. First, we used murine macrophage cell line RAW 264.7 and dendritic cell line DC2.4 to investigate the effects of LP33 on modulating cytokine productions via ELISA and RT-PCR analysis. LP33 induced IL-12, IL-10 and TGF-β productions in RAW 264.7 cells and IL-10 messenger RNA expression in DC2.4 cells in a does-dependent manners. Second, we sought to investigate the effects of Lactobacillus paracasei 33 yogurts in a mouse model of allergic airway inflammation. BALB/c mice were treated with two different doses of LP33, 3x106 CFU/700 μl and 9x106 CFU/700 μl, respectively, via gavaging needles for two weeks daily before Dermatophoides pteronyssinus (Der p) allergen sensitization and for another two weeks during sensitization and allergen challenge. The results showed that 9x106 CFU LP33 yogurts-treated mice exhibited decreased airway hyperresponsiveness and less influx of total leukocytes, monocytes and lymphocytes to the airway as compared to non-treated Der p-sensitized mice. The histological analysis also showed attenuated peribronchial inflammation and lung epithelial cells damage. Moreover, the Th1 cytokine IL-12 production in bronchoalveolar lavage fluid (BAL), Der p-specific IgG2a in sera, and IFN-γ production in Der p -stimulated splenocytes were significantly increased. In contrast, treatment of 3x106 CFU LP33 yogurts only elevated IFN-γ production in Der p-stimulated splenocytes and reduced the splenocyte proliferation activity. Taken together, our results showed that oral administration with Lactobacillus paracasei 33 yogurts can attenuate allergic airway inflammation by enhancing Th1 immune response.

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