Human interleukin 10 gene therapy decreases the severity and mortality of lethal pancreatitis in rats.
BACKGROUND
Studies have proven the validity of interleukin-10 (IL-10) in the treatment of experimental pancreatitis. Prophylactic human IL-10 (hIL-10) gene treatment attenuated the severity in cerulein models. Our research aims to study whether the therapeutic hIL-10 gene could decrease both severity and mortality in a lethal pancreatic model.


METHODS
Severe acute pancreatitis (SAP) was induced by sodium taurocholate. A plasmid-hIL-10 construct (pcDNA3-hIL-10) complexed with cationic liposomes was administered to SAP rats by a single intraperitoneal injection. Levels of hIL-10 in the pancreas, liver, and lungs were determined by ELISA kits. The severity of pancreatitis was assessed in terms of serum amylase, histology, and tissue tumor necrosis factor alpha (TNF-alpha). Mortality, observed for 7 days, was evaluated for gene therapy or control groups.


RESULTS
After hIL-10 gene therapy, hIL-10 levels in the pancreas, liver, and lungs increased significantly and the serum amylase, tissue TNF-alpha, and histological changes in pancreas, liver, and lungs decreased markedly. Therefore, mortality was significantly reduced in the hIL-10 gene therapy group, in which 70% of rats survived in the 7-day observation, while only 10% survived in untreated groups (P < 0.05).


CONCLUSIONS
We found that liposome/hIL-10 gene therapy decreased severity and mortality in SAP, even carried out after SAP establishment, predicting a more convenient shift to clinical applications.
Zou
Wei-Guo
WG
Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.
Wang
Dan-Song
DS
Lang
Ming-Fei
MF
Jin
Da-Yong
DY
Xu
De-Hua
DH
Zheng
Zhong-Cheng
ZC
Wu
Zhao-Han
ZH
Liu
Xin-Yuan
XY
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D002756:Cholagogues and Choleretics; D015316:Genetic Therapy; D006801:Humans; D007274:Injections, Intraperitoneal; D016753:Interleukin-10 / Q000235:genetics*; D008081:Liposomes; D008099:Liver / Q000737:chemistry / Q000166:cytology; D008168:Lung / Q000737:chemistry / Q000166:cytology; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000473:pathology; D010195:Pancreatitis / Q000139:chemically induced / Q000401:mortality* / Q000628:therapy*; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D013656:Taurocholic Acid; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D002756:Cholagogues and Choleretics; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013656:Taurocholic Acid; D000681:Amylases