Anti-inflammatory effects of tacrolimus in a rat model of acute pancreatitis.
The present study investigated the treatment effects of the immunosuppressive agent, tacrolimus (FK506), on rats with acute necrotizing pancreatitis (ANP).


METHODS
We used the taurocholate-induced model of acute necrotizing pancreatitis (ANP) in rats that were divided into seven groups: The sham group included animals that underwent sham operations. The ANP group contained ANP rats induced by taurocholate. The tacrolimus groups contained ANP rats treated with tacrolimus at three different time points (prior to the induction of ANP, immediately after the induction of ANP, one hour after the induction of ANP). The somatostatin group included ANP rats treated with somatostatin. The glucocorticoids group contained ANP rats treated with glucocorticoids. At 3, 6 and 12 hours after the induction of taurocholate, blood samples were collected for TNF-alpha, IL-1beta and amylase assays, and lung and pancreas tissues were harvested for histopathological study and edema evaluation.


RESULTS
Tacrolimus administered prior to the induction of ANP and immediately after the induction of ANP caused a significant decrease in the twenty two-hour mortality rate (p<0.05). However, tacrolimus did not decrease the mortality rate when administered one hour after the induction of ANP (p>0.05). Treatment with all three drugs (tacrolimus, somatostatin and glucocorticoids) resulted in a significant decrease of serum amylase, lung edema, and serum TNF-alpha and IL-1beta levels. Pancreatic and pulmonary morphological alterations were improved.


CONCLUSIONS
Tancrolimus can decrease pancreatic and pulmonary injury. The effect of tacrolimus treatment is the same as that of somatostain and glucocroticoids. It is also more effective to administer the drug earlier.
Liu
Chaoxu
C
Xijing Hospital of Digestive Disease, Fourth Military Medical University, Chang Le West Road 15, Xi'an 710032, P. R. China.
Dou
Kefeng
K
Dou
Chunqing
C
Liu
Jianhua
J
Zhao
Qingchuan
Q
D000681:Amylases / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001201:Ascites / Q000188:drug therapy; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016559:Tacrolimus / Q000494:pharmacology* / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D000681:Amylases; D016559:Tacrolimus