title: Human interleukin 10 gene therapy decreases the severity and mortality of lethal pancreatitis in rats.
abstract: 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.
authors.affiliation: Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, 200031, China.
authors.forename: Wei-Guo
authors.initials: WG
authors.lastname: Zou
authors.forename: Dan-Song
authors.initials: DS
authors.lastname: Wang
authors.forename: Ming-Fei
authors.initials: MF
authors.lastname: Lang
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Jin
authors.forename: De-Hua
authors.initials: DH
authors.lastname: Xu
authors.forename: Zhong-Cheng
authors.initials: ZC
authors.lastname: Zheng
authors.forename: Zhao-Han
authors.initials: ZH
authors.lastname: Wu
authors.forename: Xin-Yuan
authors.initials: XY
authors.lastname: Liu
mesh_terms: 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
chemical_list: D002756:Cholagogues and Choleretics; D008081:Liposomes; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D013656:Taurocholic Acid; D000681:Amylases