Brief Articles
Copyright ©2009 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Apr 28, 2009; 15(16): 2032-2037
Published online Apr 28, 2009. doi: 10.3748/wjg.15.2032
Effect of 5-FU on modulation of disarrangement of immune-associated cytokines in experimental acute pancreatitis
Xiao-Li Chen, Sang-Zhu Ciren, Hui Zhang, Li-Geng Duan, Alexander J Wesley
Xiao-Li Chen, Sang-Zhu Ciren, Hui Zhang, Li-Geng Duan, Department of General Surgery, The Huaxi Hospital, Medical Center, University of Sichuan, Chengdu 610041, China
Alexander J Wesley, Department of Surgery, Transplantation Division, University of Cincinnati Medical Center, Cincinnati OH 45267-0558, United States
Author contributions: Chen XL designed this study, coordinated the experiment and was the primary writer of this manuscript; Ciren SZ, Zhang H, Duan LG performed the experiment and took part in writing the manuscript. Wesley AJ was the tutor of this study and revised the manuscript.
Correspondence to: Xiao-Li Chen, MD, Department of General Surgery, The Huaxi Hospital, Huaxi Medical Center, University of Sichuan, Wainan guoxuexiang 34#, Chengdu 610041, China.
Telephone: +86-28-85422868
Fax: +86-28-85534151
Received: September 2, 2008
Revised: March 13, 2009
Accepted: March 20, 2009
Published online: April 28, 2009

AIM: To investigate the effects of 5-Fluorouracil (5-FU) on modulation of pro-inflammatory and anti-inflammatory cytokines in acute pancreatitis and the mechanism of it in the treatment of acute pancreatitis.

METHODS: Male Sprague Dawley rats were assigned to 3 Groups: Group A, sham operated rats as controls (n = 7); Group B, acute pancreatitis induced by ductal injection with 5% sodium cholate at a volume of 1.0 mL/kg without any other treatment; Group C, after the pancreatitis was induced as in Group B, the rats were injected intravenously with 5-FU 40 mg/kg. The animals in Groups B and C were killed at 2, 6 and 24 h after operation (n = 7), and blood samples were taken for measurement of tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) (by bioassay), and interleukin-10 (IL-10), transforming growth factor-β (TGF-β) (by ELISA). The wet weight of pancreatic tissue, serum amylase levels and white blood cells were also measured.

RESULTS: Four rats in Group B and one in Group C died after pancreatitis was induced. Both pro-inflammatory cytokines (TNF-α, IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10, TGF-β) at 24 h increased significantly (P < 0.05) in rats of Group B. After treatment with 5-FU, TNF-α, IL-1, and IL-6 in serum of rats of Group C were inhibited at 2 and 6 h after operation (P < 0.05), and IL-10, TGF-β were inhibited at 24 h compared to Group B (P < 0.05). Obvious improvements in the severity of the acute pancreatitis, including the amylase levels, wet weight of pancreatic tissue and neutrophil counts, were also observed after treatment with 5-FU.

CONCLUSION: 5-FU is an anti-metabolic and immunosuppressive agent which can minimize the abnormal immune cytokine response and relieve the pathophysiological disorders associated with experimental acute pancreatitis.

Keywords: Pancreatitis, Cytokines, Systemic inflammatory response syndrome, 5-Fluorouracil