- 學位論文
慢性鼻竇炎病人血清中相關細胞激素濃度之變化與疾病嚴重度之相關性
The Change of Serum levels of cytokines profile and their relations with disease severity in patients with chronic rhinosinusitis
摘要
慢性鼻竇炎為一在全球非常普遍的疾病，主要為相關鼻竇區域的慢性發炎反應，然其詳細的病因及發生機轉仍不清楚。顯微鏡下有時可見以嗜酸性球為主的鼻竇黏膜發炎細胞浸潤，先前研究指出慢性鼻竇炎的病因可能與微生物感染、過敏原刺激及宿主本身的免疫反應有關。趨化激素eotaxin及RANTES已證實可吸引嗜酸性球至發炎部位，而介白質IL-21主要表現在人類活化的CD4+ T細胞上，有調控免疫細胞反應及過敏相關抗體IgE的功能。本實驗即試圖了解RANTES, eotaxin及IL-21在慢性鼻竇炎併鼻息肉病人血液中的表現情形其與疾病嚴重度的相關性，以鼻竇電腦斷層評估Lund-McKay法，鼻竇內視鏡鼻瘜肉嚴重程度指標Lund-Kennedy法，及評估慢性鼻竇炎之鼻竇骨壁之發炎程度Global Osteitis Scoring Scale (GOSS)做為臨床嚴中度評估。此外，我們也分離出正常人及慢性鼻竇炎病人之周邊血液單核細胞 (PBMC)，以免疫刺激因子處理，取培養液及分離細胞分析其IL-21蛋白質及RNA之表現量。首先分析血清中IgE的含量及上述細胞激素的表現，並藉由鼻竇電腦斷層結果、鼻內視鏡及鼻竇骨壁發炎的評分量表去測量疾病的嚴重性，及其與相關細胞激素變化的關係。結果顯示eotaxin, RANTES及IL-21的濃度均較對照組為高，呈現有意義的差異(p<0.05)。臨床嚴重度則與上述細胞激素之濃度變化均呈正關，但eotaxin的相關性較強。另經免疫刺激因子作用後，慢性鼻竇炎病人之周邊血液單核細胞培養液之IL-21之濃度較正常人高，但IL-21 mRNA之表現則無明顯差異。IL-21, eotaxin, RANTES等細胞激素或趨化激素在慢性鼻竇炎之致病機轉仍有待釐清，然其與該疾病嚴重度之相關性或可作為以藥物或手術治療的預後指標，並對難治極易復發之慢性鼻竇炎病人可發展出新的篩選方式，追蹤方法及治療模式。
並列摘要
Chronic rhinosinusitis (CRS) is a prevalent disease worldwide and affecting people of all age groups. Its pathogenesis is proposed to be related to bacterial infection, allergic response or host defense system, but the exact mechanisms are still under investigation. Histologically, inflammatory cell infiltrations of nasal mucosa predominated by eosinophils are characteristic for such disease, which might be driven by the chemotactic activity of chemokines specific for eosinophils. CC-chemokine eotaxin and RANTES (regulated on activation normal T cell expressed and secreted) have been postulated to be involved in the eosinophils recruitment.Interleukin-21(IL-21) is mainly expressed in activated human CD4+ T cells and has potent regulatory effects on cells of the immune system. To explore their possible roles in CRS with nasal polyps, we examined the serum concentration of eotaxin, RANTES, immunoglobulin E (IgE), IL-21 by enzyme-linked immunosorbent assay (ELISA)from CRS patients compared with those of healthy controls and correlated these results to the severity of disease burden graded by preoperative sinus computerized tomography(CT) imaging﹐ nasal endoscope findings and global osteitis scoring scale (GOSS).We also analyzed the protein and mRNA expression of IL-21 in peripheral blood mononuclear cells (PBMC) stimulated by anti-CD3/CD28 or phyto- agglutinin (PHA) by ELISA and real-time quantitative polymerase chain reaction (RT-qPCR). Our results showed that significantly increased level of serum RANTES, eotaxin and IL-21 was observed in patients suffering from CRS compared to that of control. Besides, RANTES, eotaxin and IL-21 levels were significantly correlated with the disease severity in CRS patients, and eotaxin was the most potent indicator among them. Besides, in the PBMC of CRS patients after stimulation, IL-21 protein level was elevated compared to controls, but the mRNA expression was not different significantly. It is presumed that these cytokines levels can be used to monitor disease progression and attenuation.
並列關鍵字
chronic rhinosinusitis ； nasal polyp ； IgE ； eotaxin ； RANTES ； IL-21 ； eosinophil ； PBMC ； disease severity ； Lund-McKay score ； Lund-Kennedy score ； GOSS參考文獻
延伸閱讀
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