- 期刊
COX-2抑制劑阻礙口服免疫耐受性之形成
Abrogation of Oral Tolerance Induction by COX-2 Inhibitors
摘要
研究背景：口服免疫耐受性使我們免於食物過敏反應。轉殖鼠實驗顯示3A9小鼠口服HEL（hen egg lysozyme）會形成口服免疫耐受性；但是，如同時給HEL與COX-2抑制劑，卻會造成3A9小鼠的小腸對HEL產生嚴重食物過敏反應。研究目的：COX-2抑制劑是否會影響正常的非轉殖鼠之口服免疫耐受性之形成。研究方法：BALB/c小鼠在餵食1ml蛋清或PBS的4及1小時前，分別腹腔注射62.5μg indomethacin或50μg rofecoxib各1次。7天後，再分別腹腔注射10 μg ovomucoid（OVO）與4mg alum加以致敏。致敏後7至14天，分別取小鼠血清或脾臟細胞，進行特異性抗體和細胞激素分析。研究結果：餵食蛋清的小鼠會誘發口服免疫耐受性，對OVO有較低的IgE, IgG1和IgG抗體。但餵食蛋清前注射indomethacin或rofecoxib的小鼠，則缺乏口服免疫耐受性，其抗體不但沒有降低，而且致敏後第7天的IgG1和IgG抗體出現次發性升高反應。此外，檢測脾臟細胞的增生反應和IL-4分泌量，發現只有餵食蛋清的小鼠會因口服免疫耐受性而降低，而餵食蛋清前給予COX-2抑制劑的小鼠則沒有降低。研究結論：COX-2抑制劑會阻礙正常小鼠口服免疫耐受性之形成。由於抑制發炎藥物NSAIDs非常普遍，對COX-2有選擇性抑制作用的新藥也已上市。因此，必須告知用藥人在吃COX-2抑制劑時，要避免同時吃含蛋白質食物，以免妨礙口服免疫耐受性之形成。
並列摘要
Background: Oral tolerance is readily induced in 3A9 TCR transgenic mice with TCR specific for hen egg lysozyme (HEL), but oral sensitization was prominent in these mice when COX-2 inhibitors were co-administered with HEL.Objective: Whether COX-2 inhibitors can abrogate oral tolerance induction in conventional mice has not been elucidated.Methods: Indomethacin (62.5μg) and rofecoxib (50μg) were i.p. injected respectively 4 h and 1 h before oral administration of 1 ml of egg white (EW) or PBS to BALB/c mice. One week later, they were i.p. sensitized with 10 μg ovomucoid (OVO) adsorbed onto 4 mg alum respectively. They were then bled 7 or 14 days later. Some of their spleen were collected 10 days after sensitization.Results: Oral tolerance of IgE, IgG1 and IgG responses to OVO was induced in mice fed EW only, but it was abrogated in EW-fed mice receiving indomethacin or rofecoxib. Moreover, priming of IgG and IgG1 responses was found 7 days after sensitization. In addition, oral tolerance of spleen cell proliferation and IL-4 production was induced in EW-fed mice, but it was not in those receiving Indomethacin or rofecoxib.Conclusion: The induction of oral tolerance can be abrogated by cyclooxygenase 2 (COX-2) inhibitors. Since COX-2 inhibitors are becoming popular, it is necessary to warn patients to avoid taking them together with first encountered protein diets.
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