Effects of thalidomide in experimental models of post-endoscopic retrograde cholangiopancreatography pancreatitis.
BACKGROUND
Tumor necrosis factor-alpha (TNF-alpha) plays a central role in the pathogenesis of acute pancreatitis and related systemic complications. The authors hypothesized that it may also play an important role in the development of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). The aim of the study was to evaluate the effectiveness of thalidomide, an immunomodulator that exerts an inhibitory action on TNF-alpha by enhancing mRNA degradation, in reducing post-ERCP pancreatitis in a rat model.


METHODS
A total of 200 mg/kg thalidomide was given intragastric once a day (total 8 days) before the experimental models of post-ERCP pancreatitis were established. After 24 h, histology and edema of pancreas, serum amylase, and TNF-alpha mRNA in the pancreatic tissue were evaluated.


RESULTS
Intraductal contrast infusion caused increases in serum amylase, edema, histological grade, and TNF-alpha mRNA of pancreas. The prophylactic use of thalidomide significantly reduced serum amylase, pancreatic edema and the histologic grade of pancreatitis accompanied by a decrease in mRNA expression of TNF-alpha in the pancreatic tissue.


CONCLUSIONS
Prophylactic intragastric administration of thalidomide provides a protective effect in post-ERCP pancreatitis. The mechanism of the protective effects of thalidomide seems to be the reduction of expression of TNF-alpha mRNA in pancreatic tissue.
Xiong
Guang-Su
GS
Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University, Shanghai Institute of Digestive Disease, Shanghai, China.
Wu
Shu-Ming
SM
Wang
Zhen-Hua
ZH
Mo
Jian-Zhong
JZ
Xiao
Shu-Dong
SD
D000818:Animals; D002760:Cholangiopancreatography, Endoscopic Retrograde / Q000009:adverse effects*; D004195:Disease Models, Animal; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D010195:Pancreatitis / Q000209:etiology* / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013792:Thalidomide / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D013792:Thalidomide