Heat shock response is associated with protection against acute interstitial pancreatitis in rats

We recently reported that hyperthermia induces pancreatic expression of heat shock proteins (HSPs), particularly HSP70 isoforms, and protects against cerulein pancreatitis. We have now studied whether a double hyperthermia amplifies these effects and whether hyperthermia also protects against dibutyltin dichloride (DBTC)-induced pancreatitis. A further aim was to examine whether hyperthermia induces changes in transforming growth factor-beta1 (TGF-beta1). Following pretreatment without or with a single or double hyperthermia, pancreatitis was induced by application of cerulein or DBTC. Pancreatic HSP and TGF-beta1 expression were studied by immunoblotting. Pancreas injury was assessed by light microscopy and serum pancreatic enzyme activity. Hyperthermia as well as DBTC induced HSP72, whereas cerulein did not. A double hyperthermia led to a further increase in HSP72 compared to a single heat stress. In both models, hyperthermia significantly reduced pancreatic injury. Although a double hyperthermia slightly decreased the severity of cerulein pancreatitis compared to a single heat treatment, an improved pancreas protection against DBTC cytotoxicity was not achieved. We also found that hyperthermia induces the expression of TGF-beta1. In conclusion, hyperthermia preconditioning exerts protective effects against two pathophysiologically different types of pancreatitis by a mechanism that involves the up-regulation of HSP70 isoforms as well as TGF-beta1.