Norman J G, Fink G W, Denham W, Yang J, Carter G, Sexton C, Falkner J, Gower W R, Franz M G
Department of Surgery, University of South Florida, Tampa 33612, USA.
Dig Dis Sci. 1997 Aug;42(8):1783-8. doi: 10.1023/a:1018886120711.
Our purpose was to determine if cytokines are produced systemically during acute pancreatitis. Proinflammatory cytokines are elevated during acute pancreatitis and have been implicated in the progression of pancreatitis-associated multiple organ dysfunction. Whether these mediators are produced within all tissues or very few specific organs is not known. Edematous pancreatitis was induced in adult male mice by IP injection of cerulein. Necrotizing pancreatitis was induced in young female mice by feeding a choline-deficient, ethionine supplemented diet. Animals were sacrificed as pancreatitis worsened, with multiple organs prepared for tissue mRNA and protein analysis by RT-PCR and immunoblotting. Pancreatitis severity was established by histologic grading and serum amylase and lipase. There was no cytokine mRNA or protein detectable prior to the induction of pancreatitis. Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1-beta (IL-1 beta) mRNA and protein were detected within the pancreas early in the course of pancreatitis in both models, coinciding with the development of hyperamylasemia (both P < 0.001). Interleukin-6 was produced in the pancreas after pancreatitis was more fully developed (P < 0.001). IL-1 beta and TNF-alpha were subsequently produced in large amounts in lung, liver, and spleen but never within kidney, cardiac muscle, or skeletal muscle. A significant delay between pancreatic and distant organ cytokine production was always observed. It is concluded that proinflammatory cytokines are produced within the pancreas and within organs known to develop dysfunction during severe pancreatitis. Cytokine production is tissue specific, correlates with disease severity, and occurs within the pancreas first and subsequently within distant organs.
我们的目的是确定在急性胰腺炎期间细胞因子是否会在全身产生。促炎细胞因子在急性胰腺炎期间会升高，并与胰腺炎相关的多器官功能障碍的进展有关。尚不清楚这些介质是在所有组织中产生还是仅在极少数特定器官中产生。通过腹腔注射雨蛙素在成年雄性小鼠中诱导水肿性胰腺炎。通过喂食缺乏胆碱、补充乙硫氨酸的饮食在年轻雌性小鼠中诱导坏死性胰腺炎。随着胰腺炎恶化，处死动物，将多个器官用于通过逆转录聚合酶链反应（RT-PCR）和免疫印迹进行组织mRNA和蛋白质分析。通过组织学分级以及血清淀粉酶和脂肪酶确定胰腺炎的严重程度。在诱导胰腺炎之前未检测到细胞因子mRNA或蛋白质。在两种模型中，胰腺炎病程早期胰腺内均检测到肿瘤坏死因子-α（TNF-α）和白细胞介素-1-β（IL-1β）的mRNA和蛋白质，这与高淀粉酶血症的出现同时发生（两者P<0.001）。胰腺炎充分发展后，胰腺中产生白细胞介素-6（P<0.001）。随后，肺、肝和脾中大量产生IL-1β和TNF-α，但肾、心肌或骨骼肌中从未产生。胰腺和远处器官细胞因子产生之间始终存在明显延迟。结论是促炎细胞因子在胰腺内以及已知在重症胰腺炎期间会发生功能障碍的器官内产生。细胞因子的产生具有组织特异性，与疾病严重程度相关，首先在胰腺内发生，随后在远处器官内发生。
