Effect of 5-FU on modulation of disarrangement of immune-associated cytokines in experimental acute pancreatitis.
OBJECTIVE
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-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 (IL-6) (by bioassay), and interleukin-10 (IL-10), transforming growth factor-beta (TGF-beta) (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-alpha, IL-1, IL-6) at the 2 and 6 h period and the anti-inflammatory cytokines (IL-10, TGF-beta) at 24 h increased significantly (P < 0.05) in rats of Group B. After treatment with 5-FU, TNF-alpha, 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-beta 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.


CONCLUSIONS
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.
Chen
Xiao-Li
XL
Department of General Surgery, The Huaxi Hospital, Huaxi Medical Center, University of Sichuan, Wainan guoxuexiang 34#, Chengdu, China. zean_z@yahoo.com.cn
Ciren
Sang-Zhu
SZ
Zhang
Hui
H
Duan
Li-Geng
LG
Wesley
Alexander J
AJ
D000818:Animals; D016207:Cytokines / Q000276:immunology*; D005472:Fluorouracil / Q000627:therapeutic use*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D010195:Pancreatitis / Q000188:drug therapy / Q000276:immunology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D016207:Cytokines; D007166:Immunosuppressive Agents; D005472:Fluorouracil