TNF-α Regulating Interleukin-33 Induces Acute Pancreatic Inflammation in Rats

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.

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.

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.

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.