Bentrem David J, Joehl Raymond J
Department of Surgery, Northwestern University Feinberg School of Medicine, and Surgical Service, VA Chicago Health Care System, Illinois, USA.
Crit Care Med. 2003 Aug;31(8 Suppl):S582-9. doi: 10.1097/01.CCM.0000081428.35729.73.
The pathophysiology of acute pancreatitis represents a diverse mix of congenital, hereditary, and acquired problems associated with or causing acute pancreatic inflammation. Acute pancreatitis is characterized by acinar cell injury that may involve regional and systemic inflammatory responses. The systemic manifestations of acute pancreatitis are responsible for the majority of pancreatitis-associated morbidity and are due to the actions of specific inflammatory cytokines. This report summarizes this pancreatic injury, the role of cytokines in the pathogenesis of acute pancreatitis, and the pancreatic healing response that follows.
A comprehensive literature review of experimental pancreatitis as well as reports of cytokine involvement and healing response during clinical pancreatitis was performed.
Histamine release, bradykinin generation, and cytokine release play a significant role during acute pancreatic inflammation. Following an experimental insult, there is rapid expression of tumor necrosis factor-alpha, interleukin-6, interleukin-1, and chemokines by pancreatic acinar cells and/or transmigrated leukocytes. Preventing the action of these mediators has a profound beneficial effect in experimental animals. Pancreatic fibrosis is a central histologic response after pancreatitis. Transient collagen deposition with acinar necrosis occurs in acute pancreatitis; in chronic pancreatitis, permanent and disorganized pancreatic fibrosis and parenchymal cell atrophy occur.
Inflammatory mediators are responsible for the systemic manifestations of acute pancreatitis and the associated distant organ dysfunction. After the acute injury, regeneration or pancreatic repair is characterized by decreased release of proinflammatory mediators and decreased infiltrating inflammatory cells. Differentiation and proliferation of pancreatic myofibroblasts or "stellate" cells may be responsible for increased extracellular matrix production. The predictable nature in which the inflammation and fibrosis are produced may stimulate novel approaches to disease treatment.
急性胰腺炎的病理生理学表现为与急性胰腺炎症相关或导致急性胰腺炎症的先天性、遗传性和后天性问题的多种组合。急性胰腺炎的特征是腺泡细胞损伤，可能涉及局部和全身炎症反应。急性胰腺炎的全身表现是大多数胰腺炎相关发病的原因，并且是特定炎症细胞因子作用的结果。本报告总结了这种胰腺损伤、细胞因子在急性胰腺炎发病机制中的作用以及随后的胰腺愈合反应。
对实验性胰腺炎以及临床胰腺炎期间细胞因子参与和愈合反应的报告进行了全面的文献综述。
组胺释放、缓激肽生成和细胞因子释放在急性胰腺炎症中起重要作用。在实验性损伤后，胰腺腺泡细胞和/或迁移的白细胞会迅速表达肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1和趋化因子。在实验动物中，阻止这些介质的作用具有深远的有益效果。胰腺纤维化是胰腺炎后的主要组织学反应。急性胰腺炎时会出现伴有腺泡坏死的短暂胶原沉积；在慢性胰腺炎中，会出现永久性且紊乱的胰腺纤维化和实质细胞萎缩。
炎症介质是急性胰腺炎全身表现及相关远处器官功能障碍的原因。急性损伤后，再生或胰腺修复的特征是促炎介质释放减少和浸润性炎症细胞减少。胰腺肌成纤维细胞或“星状”细胞的分化和增殖可能是细胞外基质产生增加的原因。炎症和纤维化产生的可预测性质可能会激发新的疾病治疗方法。
