Wittel Uwe A, Rau Bettina, Gansauge Frank, Gansauge Susanne, Nussler Andreas K, Beger Hans G, Poch Bertram
Department of General, Visceral, and Transplantation Surgery, University of Freiburg, 79106 Freiburg, Germany.
Dig Dis Sci. 2004 Aug;49(7-8):1348-57. doi: 10.1023/b:ddas.0000037833.16433.77.
The outcome of severe acute pancreatitis is determined by the development of the systemic inflammatory response and subsequent multiorgan dysfunction. Using the taurocholate-induced model of acute pancreatitis in rats, we investigated the relationship between early polymorphonuclear (PMN)-mediated pancreatic tissue damage and the systemic inflammatory response. The respiratory burst of PMN leukocytes was increased in animals with acute pancreatitis and was reduced by anti-ICAM-1 antibody and oxygen radical scavenger treatment after 24 hr. In acute pancreatitis a reduced number of peripheral helper T cells was evident, most likely due to L-selectin-mediated increased lymphocyte homing. After 24 hr the CD45RC(high)/CD45RC(low) ratio of helper T cells, a critical factor in T cell-mediated disease was increased due to a reduction of regulatory CD45RC(low) cells. Only the treatment with anti-ICAM-1 mAb affected these changes, indicating that immunological changes in necrotizing pancreatitis are only in part affected by early PMN leukocyte-mediated pancreatic damage.
重症急性胰腺炎的预后取决于全身炎症反应的发展及随后的多器官功能障碍。利用牛磺胆酸盐诱导的大鼠急性胰腺炎模型,我们研究了早期多形核白细胞(PMN)介导的胰腺组织损伤与全身炎症反应之间的关系。急性胰腺炎动物中PMN白细胞的呼吸爆发增加,24小时后抗ICAM-1抗体和氧自由基清除剂治疗可使其降低。在急性胰腺炎中,外周辅助性T细胞数量明显减少,这很可能是由于L-选择素介导的淋巴细胞归巢增加所致。24小时后,由于调节性CD45RC(low)细胞减少,辅助性T细胞的CD45RC(high)/CD45RC(low)比值升高,这是T细胞介导疾病中的一个关键因素。只有抗ICAM-1单克隆抗体治疗影响了这些变化,表明坏死性胰腺炎中的免疫变化仅部分受早期PMN白细胞介导的胰腺损伤影响。