Adenoviral transfer of human interleukin-10 gene in lethal pancreatitis.
OBJECTIVE
To evaluate the therapeutic effect of adenoviral-vector-delivered human interleukin-10 (hIL-10) gene on severe acute pancreatitis (SAP) rats.


METHODS
Healthy Sprague-Dawley (SD) rats were intraperitoneally injected with adenoviral IL-10 gene (AdvhIL-10), empty vector (Adv0) or PBS solution. Blood, liver, pancreas and lung were harvested on the second day to examine hIL-10 level by ELISA and serum amylase by enzymatic assay. A SAP model was induced by retrograde injection of sodium taurocholate through pancreatic duct. SAP rats were then administered with AdvhIL-10, Adv0 and PBS solution by a single intraperitoneal injection 20 min after SAP induction. In addition to serum amylase assay, levels of hIL-10 and tumor necrosis factor-alpha (TNF-alpha) were detected by RT-PCR, ELISA and histological study. The mortality rate was studied and analyzed by Kaplan-Meier and log rank analysis.


RESULTS
The levels of hIL-10 in the pancreas, liver and lung of healthy rats increased significantly after AdvhIL-10 injection (1.42 ng/g in liver, 0.91 ng/g in pancreas); while there was no significant change of hIL-10 in the other two control groups. The concentration of hIL-10 was increased significantly in the SAP rats after AdvhIL-10 injection (1.68 ng/g in liver, 1.12 ng/g in pancreas) compared to the other two SAP groups with blank vector or PBS treatment (P<0.05). The serum amylase levels remained normal in the AdvhIL-10 transfected healthy rats. However, the serum amylase level was significantly elevated in the other two control SAP rats. In contrast, serum amylase was down-regulated in the AdvhIL-10 treated SAP groups. The TNF-alpha expression in the AdvhIL-10 treated SAP rats was significantly lower compared to the other two control SAP groups. The pathohistological changes in the AdvhIL-10 treated group were better than those in the other two control groups. Furthermore, the mortality of the AdvhIL-10 treated group was significantly reduced compared to the other two control groups (P<0.05).


CONCLUSIONS
Adenoviral hIL-10 gene can significantly attenuate the severity of SAP rats, and can be used in the treatment of acute inflammation process.
Chen
Zi-Qian
ZQ
Department of Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai 200025, China.
Tang
Yao-Qing
YQ
Zhang
Yi
Y
Jiang
Zhi-Hong
ZH
Mao
En-Qiang
EQ
Zou
Wei-Guo
WG
Lei
Ruo-Qing
RQ
Han
Tian-Quan
TQ
Zhang
Sheng-Dao
SD
D000256:Adenoviridae / Q000235:genetics*; D000681:Amylases / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D015316:Genetic Therapy; D005822:Genetic Vectors; D016753:Interleukin-10 / Q000235:genetics* / Q000627:therapeutic use; D010195:Pancreatitis / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D051381:Rats; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D000681:Amylases