口服檳榔子萃取物抑制小鼠干擾素伽瑪及抗原專一性 IgM 抗體之生成反應   全文下載

Areca Nut Extracts Attenuated Interferon-γ and Antigen-specific IgM Production in BALB/c Mice

嚼食檳榔已知是誘發口腔癌前病變和口腔癌的主要致病因子，而免疫系統的惡化與嚼食檳榔所導致的口腔疾病的發展有密切相關性。離體研究指出檳榔子萃取物會影響淋巴球及嗜中性球的功能，本實驗室先前的研究結果顯示腹腔注射檳榔子萃取物會促進小鼠發炎反應，以及影響抗原專一性免疫反應。本研究的目的在探討經口投予檳榔子萃取物對於T淋巴球媒介免疫反應之影響。檳榔子萃取物（200 mg/kg）以管胃方式，單次投予未經免疫的小鼠，對脾臟細胞以刀豆素A（concanavalinA；ConA）刺激之干擾素伽瑪的生成，具有顯著抑制作用，但對介白素-2和介白素-4則無影響。進一步我們以卵白蛋白免疫之小鼠， 每日1次經口投予9次檳榔子萃取物（200 mg/kg），結果顯示抗原專一性干擾素伽瑪及血清中IgM抗體的生成受到抑制。脾臟細胞的族群分布及代謝活性並未受到檳榔子萃取物的影響。由本實驗結果可知，經口投予檳榔子萃取物會調節抗原專一性T淋巴球的反應，由於干擾素伽瑪具有活化多種免疫細胞的作用，檳榔子抑制干擾素伽瑪的生成可能是檳榔相關口腔疾病病人免疫惡化的重要機轉之一。

Areca-nut chewing has been well established as a major risk factor for oral cancer and precancerous diseases, whose pathophysi-ology has been associated with immune deterioration. Previous studies reported that areca nut extracts (ANE) affected the functionality of lymphocytes and neutrophils in vitro. We recently showed that intraperitoneal administration of ANE modulated antigen-specific immunity and promoted inflammatory reactions in ovalbumin (OVA)-sensitized mice. The objective of the present studies was to further investigate the in vivo effect of ANE on T cell-mediated immune responses. In non-sensitized mice, a single oral dose of ANE (200 mg/kg) markedly suppressed the production of interferon (IFN)-γ by splenocytes stimulated with the T cell mitogen concanavalin A, whereas the expression of interleukin (IL)-2 or IL-4 was unaltered. In OVA-sensitized mice, daily administration of ANE (200 mg/kg) for 9 days significantly suppressed the antigen-induced production of IFN-g by splenocytes and the serum level of antigen-specific IgM. Both the cellularity and the metabolic activity of splenocytes were unaffected by the ANE treatment. Collectively, these results demonstrated that oral administration of ANE modulated antigen-specific T cell responses. As IFN-g is a key cytokine involved in the activation of various immunocompetent cells, ANE-mediated suppression of IFN-γ production may be a critical mechanism contributing to the immune deterioration associated with areca-related oral diseases.