出版年:

研究生:

林欣怡

研究生(英文姓名):

Lin Hsin-Yi

論文名稱:

鏈球菌致熱性外毒素A刺激人類週邊單核細胞產生細胞素引起發燒反應

英文論文名稱:

Streptococcal Pyrogenic Exotoxin A Acts through Release of Cytokines from Human Peripheral Blood Mononuclear Cells to Induce Fever

指導教授:

翁舷誌 博士

指導教授(英文姓名):

Dr. Won Shen-Ji

學位類別:

碩士

校院名稱:

國立成功大學　

系所名稱:

微生物暨免疫學研究所

學號:

S46861034

學年度:

87

語文別:

中文

論文頁數:

73

關鍵詞:

化膿性鏈球菌 ; 鏈球菌致熱性外毒素A ; 人類週邊單核細胞

英文關鍵詞:

Streptococcus pyogenes ; Streptococcal pyrogenic exotoxin A ;
SPEA ; Human peripheral blood mononuclear cell ;
PBMC ; anisomycin ; dexamethason ; indomethacin

被引用次數:

1

[ 摘要 ]

A群鏈球菌 (化膿性鏈球菌) 可引起人類嚴重侵襲性感染。化膿性鏈球菌可產生許多細胞外毒素，如鏈球菌致熱性外毒素A (Streptococcal pyrogenic exotoxin A, SPEA)、B及C。這些毒素有許多的生物特性，如引起發燒反應、增強內毒素休克現象以及刺激細胞素的產生。目前證明SPEA是一種超抗原。為了探討SPEA引起發燒反應中致熱性細胞素所扮演的角色，以SPEA刺激人類週邊單核細胞 (human peripheral blood mononuclear cells, PBMC) 之上清液靜脈注射兔子觀察其體溫變化及分析此上清液是否產生致熱性細胞素，如腫瘤壞死因子 (tumor necrosis factor, TNF)、第一介白質 (interleukin-1, IL-1)、第二介白質 (IL-2)、及第六介白質 (IL-6)。結果顯示，SPEA刺激PBMC的上清液靜脈注射到兔子體內，會引起劑量相關性的發燒，此上清液經70℃ 30分鐘處理後可破壞其引起兔子發燒的現象。SPEA刺激PBMC之上清液可引起兔子的發燒同時其上清液中之TNF、IL-1、IL-2及IL-6也有增加的現象，其TNF、IL-1、IL-2及IL-6在24到48小時開始產生而在72至96小時左右則達到最高量。SPEA同時加入anisomycin (蛋白質抑制劑，0.4 ug/ml)、dexamethasone (抗發炎劑及免疫抑制劑，0.4 ug/ml) 或indomethacin (COX抑制劑，100 ug/ml) 和PBMC一起培養，皆可減少SPEA刺激PBMC所產生的細胞素，且影響上清液引起兔子的發燒現象。以上實驗結果顯示，SPEA可藉由刺激PBMC產生細胞素，而引起發燒反應。

[ 英文摘要 ]

Group A streptococci (Streptococcus pyogenes, S. pyogenes) causes severe invasive infections in humans. S. pyogenes produce a number of extracellular toxins including streptococcal pyrogenic exotoxin A (SPEA), B, and C. These toxins share many biological properties, such as fever induction, ability to enhance susceptibility to endotoxic shock, and stimulation of cytokines production. SPEA is known as a superantigen. In order to explore possible roles played by pyrogenic proinflammatory cytokines in the development of SPEA fever, experiments were carried out to assess both the body temperatures in rabbits and the pyrogenic proinflammatory cytokines including tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, and IL-6 in SPEA-stimulated human peripheral blood mononuclear cell (PBMC) supernatants. The present results demonstrated that intravenous injection of the supernatants from SPEA-stimulated PBMC caused a dose-related fever in rabbits, and was destroyed by heating the supernatants at 70℃for 30 min. The levels of TNF, IL-1, IL-2, or IL-6 in the supernatants started to rise at 24 to 48 h and reached their peak levels at 72 to 96 h after SPEA-PBMC incubation. Both the fever and the increased the levels of TNF, IL-1, IL-2, or IL-6 in the supernatents from the SPEA-stimulated PBMC were decreased by incubating SPEA-PBMC with anisomycin (a protein synthesis inhibitor, 0.4 ug/ml), dexamethasone (an anti-inflammatory and immunosupressive agent inhibitor, 0.4 ug/ml), or indomethacin (a COX inhibitor, 100 ug/ml). The present results suggest that SPEA acts through release of cytokines from the PBMC to induce fever.