金傳春2006-07-252018-06-292006-07-252018-06-292003-07-31http://ntur.lib.ntu.edu.tw//handle/246246/4693嚴重臨床症狀的登革出血熱與較為輕微症狀的登革熱之免疫致病機制差異 至今尚未被釐清。本研究目的是探討登革出血熱與登革熱病人致病過程中的3 種人類化學激素(RANTES, Mig, MIP-1摯瑬敳獩 chemokines)分泌變化是否有差異性存 在，且此差異是否與登革病患臨床狀的嚴重度有所關連。 研 究群是以2002 年月至2003 年3 月高屏地區通報登革熱病例為研究對 象，並經由台灣疾病管制局確認登革出血熱病例共23 名與登革熱病例共77 名，另取46 名健康對照組作為比較,進行抽血，以流式細胞儀分析細胞表面人 類化學激素受體及酵素免疫試劑測人類化學激素分泌量，並請醫護人員進行問 卷訪談並追蹤症狀。 結果發現：（1）登革熱病患體內CD4/CD3+T 細胞比值顯著低於健康對照組 （33.19 ±2.21 vs 40.13 ±15.94,p=0.03）；（2）登革出血熱與登革熱確定病例 的人類化學激素如RANTES （各為13.69+3.46 ng/ml 與19.56+2.74 ng/ml, p=0.14 ）、Mig （各為 653.45+ 85.89 pg/ml 與664.63+ 59.60 pg/ml, p=0.23 ）均 比健康人有顯著較高的分泌量，但此兩種登革病人的MIP-1a 分泌量(各為 26.99+ 11.56 pg/ml 與38.59+ 9.86 pg/ml)卻較健康人為低（92.47 ±13.55 pg/ml, p<0.01）；（3）不同的化學激素在病程之動態分泌量有所不同,人類化學激素如 Mig 的分泌量在登革出血熱/登革熱病例急性期高於恢復期，相對地RANTE S 分泌量在登革出血熱/登革熱病例急性期卻低於恢復期。 本研究初步結果推論登革熱出血熱/登革熱病患其人類化學激素分泌變化 有差異性存在，登革出血熱病患體內人類化學激素Mig 在發燒後頭三天(感 染急性期)有較高的分泌,可能加速吸引帶有CXCR3 之T 細胞至受感染部 位，且因RANTES 有持續性的分泌,由此三者的協同作用,會增進CD8 + T 細 胞中CCR5 的表現量，進而引起相關的細胞受到傷害，結果造成病人的嚴重 出血。未來實有必要再更急性早期採集登革病人血液檢體,以整合病毒量.免 疫活化標誌與血液動態指標,以徹底明瞭登革出血熱病人的免疫致病機轉 .Mechanism of immunopathogenesis in leading to dengue hemorrhagic fever (DHF) versus mild form of dengue fever (DF) during the same epidemic has not been fully understood. The specific aims of this study were to determine whether there are differences in the levels of chemokines (RANTES, Mig and MIP-1a ) associated with hemorrhage between DHF and DF patients or clinical complications. A prospective cohort study recruited 23 DHF and 77 DF patients caused by dengue virus serotype 2 plus 46 healthy donors from Aug. 2 to Mar. 31, 2003 in Kaohsiung and Pingtung. Levels of RANTES, Mig, MIP-1a were measured in serum samples collected at both the first visit and subsequent repeated visits. Mann-Whitney U and Spearman correlation test were used to compare the relationship between above each chemokine and clinical status of DF vs DHF or hemodynamic/ biochemical laboratory results, and their kinetic changes at different time points after the onset of fever, respectively. Ratios of CD4/CD3+T cells in DF patients was lower significantly compared to healthy controls (DF patients: 33.19+ 2.21 vs healthy controls: 40.13 + 15.94, P=0.03). There were higher serum levels of RANTES ( DHF: 13.69+3.46 vs DF: 19.56+2.74, P=0.14), Mig (DHF: 653.45+ 85.89 vs DF: 664.63+ 59.60, P=0.23) and lower levels of MIP-1a (DHF: 26.99+ 11.56 vs DF: 38.59+ 9.86, P=0.56). However, serum levels of RANTES, Mig were significantly higher than healthy controls (P<0.05), whereas levels of MIP-1a in dengue patients were significantly lower than compared to healthy controls (P<0.05). The serum levels of chemokine were also compared after fever onset. Levels of Mig in DHF and DF patients after fever onset 7 days were higher ≦ than that after fever onset >7 days. In contrast, levels of RANTES in DHF and DF patients were lower after fever onset 7 days than that after fever onset >7 days.≦. In conclusion, the serum chemokine kinetic patterns of DHF were different from DF patients. These effects may lead to infected cells damages and then cause hemorrhage. A closer examination of the production of these chemokines and the activation of dengue virus infected target cells in the early phase of dengue virus infection is warranted to attain a better understanding of immunopathgenesis of DHF.application/pdf1018369 bytesapplication/pdfzh-TW國立臺灣大學公共衛生學院流行病學研究所登革熱人類化學激素人類化學激素受體登革病毒免疫免疫流行病學Dengue hemorrhagic feverInnate ImmunityImmunological ResponsesChemokineTaiwan[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/4693/1/912320B002081.pdf