The Effects of Arecoline on the Release of Cytokines Using Cultured Peripheral Blood Mononuclear Cells from Patients with Oral Mucous Diseases

檳榔素對於有嚼食檳榔習慣之黏膜下纖維化及鱗狀上皮細胞癌患者在周邊血液單核球培養中細胞激素生成影響之研究

許瀚仁(Han-Jen Hsu) ； 張基隆(Kee-Lung Chang) ； 楊奕馨(Yi-Hsin Yang) ； 謝天渝(Tien-Yu Shieh)

《The Kaohsiung Journal of Medical Sciences》 17卷4期 (2001/04) Pp. 175-182

https://doi.org/10.6452/KJMS.200104.0175

摘要

在台灣許多口腔黏膜疾病和嚼食檳榔習慣有很大的關連。檳榔塊的組成中被認為主要的致癌部分是檳榔素（arecoline, AL），檳榔鹼（arecaidine, AD），以及荖花中的黃樟素（safrole, S），此類物質是否影響免疫反應，至今無人瞭解。因此本研究欲探討口腔黏膜疾病和口腔癌病患其免疫細胞分泌之各類細胞激素是否會受檳榔塊成份的影響。實驗中分離正常人及病人血液中之單核球加以培養，以檳榔素成份刺激後，測量IL-2、TNF-α、TGF-β、IFN-γ等和細胞免疫相關細胞激素的量。結果顯示，長期嚼食檳榔而口腔黏膜仍正常者的單核球產生TGF-β的量大於未嚼食檳榔且口腔黏膜正常者；當加入檳榔素（arecoline, AL）後，未嚼食檳榔且口腔黏膜正常者的單核球產生IL-2、TNF-α、TGF-β的量皆下降。由具正常口腔黏膜但有嚼食檳榔習慣者與具正常口腔黏膜無嚼食檳榔習慣者比較各種細胞激素的生成，發現IL-2及TNF-α的生成上沒有顯著差異。IFN-γ的生成量，無嚼食檳榔者較嚼食檳榔者的量高（p＜0.02）。OSF的患者除TNF-α明顯高於正常人及SCC的患者外IL-2、TGF-β、IFN-γ皆較低。尤其是TGF-β分泌的量比正常人或SCC的患者低甚多。另外，從本研究也發現長期嚼食檳榔而仍具正常口腔黏膜者有大量的TGF-γ。TGF-β抑制IFN-γ之生成及發炎反應，可能是雖長期嚼食檳榔而仍有正常口腔黏膜的原因。本研究得知，雖然皆為口腔鱗狀上皮細胞癌，但因長期嚼食檳榔而得口腔癌者與無此習慣而得口腔癌者之間其單核球細胞產生IL-2、TNF-α、TGF-β、IFN-γ等四種細胞素的量不盡相同。兩者在IL-2、TGF-β及IFN-γ的生成雖沒有差異，但具嚼食檳榔習慣得口腔癌（SCC）者的TNF-α生成量比正常者低。而無此習慣而得口腔癌者的TNF-α則比正常者或嚼食檳榔得口腔癌者都高出甚多。嚼檳榔得口腔癌者與無嚼檳榔得口腔癌者之單核球細胞在加入檳榔素後，兩者之TNF-α表現不同。由此可知嚼食檳榔確實會影響檳榔素對免疫細胞之細胞素的分泌，而SCC與OSF的致病機轉可能因這些細胞激素表現上有明顯差異而有所不同。

並列摘要

In Taiwan there is a significant correlation between oral precancer diseases and oral cancer associated with the betel quid chewing habit. The carcinogenic components of betel quid are arecoline, arecaidine and safrole. However, it is unknown whether these substances influence the immune functions. This study investigated the effects of betel quid on the immune system using cultured peripheral blood mononuclear cells from patients with oral mucous diseases. In our experiment, mononuclear cells from 10 normal persons, 12 patients with precancer lesions, and 16 patients with squamous cell carcinoma were separated from blood samples and cultured. After stimulation by arecoline, the amounts of IL-2、TNF-α、TGF-β and IFN-γ secreted by mononuclear cells were measured using the ELISA method. The results showed that IL-2、TNF-α and TGF-β were significantly lower in mononuclear cells of normal persons as stimulated by arecoline. The TGF-β amount in cells from oral submucous fibrosis patients with betel quid chewing habit (OSF-B) was lower than normal persons or patients who had long term betel quid chewing habit but were without oral mucosal diseases (N-B), and was also lower than the squamous cell carcinoma with betel quid chewing group (SCC-B). TNF- α was significantly lower in the squamous cell carcinoma with long term betel quid chewing group (SCC-B) than in normal persons. TNF-α was significantly higher in the squamous cell carcinoma without betel quid chewing group (SCC-N) than in normal persons and SCC-B groups. In addition, IFN-γ was significantly lower in patients who had long term betel quid chewing but were without oral mucous lesions than the normal person and the OSF group. The results proved that betel quid influences cytokines production by mononuclear cells.

並列關鍵字

areca/betel quid ； oral submucous fibrosis ； SCC ； IL-2 ； TNF-α ； TGF-β ； IFN-γ