title: TNF-α Regulating Interleukin-33 Induces Acute Pancreatic Inflammation in Rats.
abstract: BACKGROUND
  Acute pancreatitis (AP) is a common disease with a high fatality rate as a result of its unclear pathogenesis. Interleukin (IL)-33 plays a role in various inflammatory conditions but its role and regulatory mechanisms in AP is still unknown.
  
  
  METHODS
  The serum levels of IL-33, sST2, TNF-α and IL-6 in AP patients were detected using ELISA. The correlations between IL-33 and TNF-α, sST2, IL-6, Ranson score and APACHE II score were investigated using Pearson correlation analysis. AP rat model was established by injecting sodium taurocholate to explore the expression of IL-33, TNF-α, sST2 and IL-6 at the early stage of AP. Expression of IL-33 and IL6 in pancreas of AP rats was determined with qRT-PCR and Western-Blot. Intravenous injection of purified TNF-α was performed to explore the regulatory mechanisms of IL-33.
  
  
  RESULTS
  Our data found that AP patients had high serum level of IL-33, sST2, TNF-α and IL-6. IL-33 was positively related with the Ranson score and APACHE II score. Similarly, sodium taurocholate induced AP rats had significantly increased serum IL-33, sST2, TNF-α and IL-6 levels, with peaks at 8 h post-operation for IL-33 and TNF-α, and 12 h for sST2 and IL-6. IL-33 mRNA and protein levels were both increased in the pancreas of AP rats. In addition, TNF-α significantly stimulated the production of IL-33 and subsequently led to an increase of IL-6.
  
  
  CONCLUSIONS
  IL-33 is elevated at the early stage of AP and correlated with AP severity. TNF-α stimulated IL-33/sST2 and subsequent increase of IL-6 may be the mechanism of IL-33 in AP.
authors.affiliation: Department of Hepatobiliary Surgery, the 1st People's Hospital of Changzhou, Changzhou, China yjiang8888@hotmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, the 1st People's Hospital of Changzhou, Changzhou, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: An
authors.affiliation: Department of Hepatobiliary Surgery, People's Hospital of Wujin, Changzhou, China.
authors.forename: Danqian
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Hepatobiliary Surgery, the 1st People's Hospital of Changzhou, Changzhou, China.
authors.forename: Baoqiang
authors.initials: B
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, the 1st People's Hospital of Changzhou, Changzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Hepatobiliary Surgery, the 1st People's Hospital of Changzhou, Changzhou, China.
authors.forename: Donglin
authors.initials: D
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D003710:Demography; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism*; D000067596:Interleukin-33 / Q000097:blood / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D010179:Pancreas / Q000473:pathology*; D010195:Pancreatitis / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D017207:Rats, Sprague-Dawley; D017472:Receptors, Interleukin-1 / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism*
chemical_list: D000067596:Interleukin-33; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; C000589812:ST2 protein, rat; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10
keywords: Acute pancreatitis; Interleukin-33; TNF-α