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細胞計劃性死亡，無論在生理或病理發展過程中，皆扮演著重要的地位。
本論文主要藉由實驗動物模式來探討敗血症對免疫系統的影響，尤其是對
胸腺的變化。我們的實驗結果發現：以腹腔注射給于小鼠革蘭氏陰性菌(
Escherichia coli,Klebsiella pneumonia 和 Psendomonas aeruginosa
），造成胸腺明顯萎縮，在給于小鼠細菌 3小時之後，其胸腺重量、胸腺
細胞數目和細胞生存率皆下降，而於 72小時降至最低點。又由凝膠電泳
實驗中亦證實：敗血症引發小鼠胸腺細胞的死亡，是經由細胞計劃性死
亡(apoptosis)的途徑。其伴隨著大約 200b.p的 DNA 片斷。進一步由免
疫螢光分析法亦證實，所減少的胸腺細胞群主要是屬於 CD4+CD8+細胞族
群，另一族群 CD4+CD8-細胞則被刺激而增加。有趣的是，革蘭氏陰性菌
所引起的敗血症亦皆能引發對脂多醣反應的小鼠(C3H/HeN)和脂多醣不反
應的小鼠(C3H/HeJ)胸腺細胞之計劃性死亡。同時,革蘭氏陽性菌(
streptoco- ccus pneumoniae)亦能引發對脂多醣不反應之小鼠的胸腺細
胞計劃性死亡。另一方面,革蘭氏陰性菌和陽性菌敗血症引發小鼠胸腺細
胞的計劃性死亡的現象能為.alpha.腫瘤壞死因子抗體(anti-TNF.alpha.
Ab)所抑制。然而 .alpha. 腫瘤壞死因子抗體僅能部分抑制革蘭氏陽性敗
血症引發小鼠胸腺細胞的計劃性死亡。又在體外實驗中,加入.alpha.型腫
瘤壞死因子亦能引發胸腺細胞的計劃性死亡。這些證據顯示,.alpha.型腫
瘤壞死因子(TNF.al pha)可能是革蘭氏陰性菌和陽性菌敗血症小鼠胸腺細
胞計劃性死亡的共同因子。我們的實驗更進一步發現：小鼠先前給予
cycloheximide或 actinomycin D 皆能抑制胸腺細胞的計劃性死亡。綜合
以上結果可知， .alpha.型腫瘤壞死因子為造成敗血症引發小鼠胸腺細胞
計劃性死亡的主要因子，而其發生過程亦需要 RNA 合成或者是蛋白質合
成的參與。
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Cell death by apoptosis mediates several important physiologic
and pathologic and processes and appeares to be intrinsically
programmed. In the study, we found that intraperitoneal
injection of Gram-negative bacteria (Escherichia coli,
Klebsiella pneumoniae, Pseudomonas aeruginosa) induces atrophy
of the thymus in mice. The thymus weight, cell number, and
viability began to decrease 3 h after E. coli injection, the
reduction reached maximum on 72 h. The thymocytes death were
also associated with DNA fragment of ~200 b.p. in ladder form.
the kinetic study on histopathology clearly revealed the
process of thymocytes death and thymic atrophy. Flow cytometric
analysis showed that CD4+CD8+ tymocytes decreased
predominantly, but was accompanied by an increase of CD4+CD8-
cells. Furthermore, Gram-negative sepsis induced apoptosis of
the thymus in LPS-responder mice (C3H/HeN) as well as in LPS-
nonresponder mice (C3H/HeJ). Interestingly, Gram-positive
bacteria (Streptococcus pneumoniae) also caused apoptosis of
the thymus in LPS-nonresponder mice. These data suggest that
not only endotoxin but also some other components derived from
bacteria can elicit apoptosis of the thymocytes in mice.
Furthermore, anti-TNF.alpha. Ab complete inhibit Gram-negative
sepsis-induced apoptosis.Gram- negative E. coli induced serum
TNF.alpha. peak at 1 h, while Gram-positive S. pneumoniae at
6-9 h. Moreover, mouse TNF.alpha. alsoenhanced thymocyte
apoptosis in in vitro culture thymocyte induced apoptosis. Our
results further showed pretreatment with actinomycin D,
cycloheximide and IVIG could inhibit the E.coli- induced
thymocyte apoptosis. This suggests that TNF.alpha. is a common
mediator involved in Gram-negative or Gram-positive bacteria
induced apoptosis of the thymocytes in mice and protein or RNA
synthesis were required for this apoptosis.
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