Stress and acute biliary pancreatitis

Accessible online at: www.karger.com/pan According to Selye’s [1] classic work, the general adaptation syndrome in response to stress involves a complex neurohumoral regulation: the release of ACTH and corticosteroids combined with catecholamine discharges and other factors resulting in gastric ulcerations because of disequilibrium between aggressive and defensive (cytoprotective) mechanisms. Overstimulation of these factors may worsen some diseases such as acute biliary pancreatitis, which per se is a stressful situation that disturbs biliopancreatic outflow and the autonomous nervous system as well as duodenopancreatic feedback regulation. Indeed, stress-induced gastric and duodenal ulceration is frequent in acute biliary pancreatitis with severe cholangitis, although the literature about the frequency of stress ulcers caused by an acute pancreatitis is rare and mostly of older date [2]. A combination of the two situations can worsen the outcome of biliary pancreatitis, as was demonstrated by the extensive experimental work of CosenBinker et al. in this issue of Pancreatology. However, short-term stress induction before pancreatitis did not worsen but slightly ameliorated the severity parameters of the inflammatory process in parallel to increasing serum corticosterone levels. Recovery from stress situation releases a group of acute-phase proteins such as heat shock proteins (HSPs), represented by HSP72 in this study. These are highly conserved, ubiquitous and functionally related proteins that play an essential part in cell survival. Following stress conditions, many cellular proteins become partially or completely denatured or malfolded. HSPs recognize this, bind to the damaged proteins and stabilize and refold them. Cells subjected to a mild, sublethal stress event sufficient to increase the levels of HSPs are able to survive a subsequent more serious stress event. HSP preinduction is known to protect the pancreas against cerulein-induced pancreatitis in rats [3]. Water immersion pretreatment and possibly HSP60 and HSP72 exert a definite protective effect in mild pancreatitis, but this was not seen in more severe acute pancreatitis models [4]. Timing of stress induction is important to achieve the beneficial effect of HSPs as demonstrated by the experiments of Cosen-Binker et al. (experiments 21–24): when animals underwent the same short-term stress after the acute biliary pancreatitis had been completed, all of them died between 5 and 8 h after the ‘bilio-pancreatic-duct outlet exclusion-closed duodenal loop’ maneuver. This fact points to the clinical relevance of HSP induction treatment and also underlines the multifactorial nature of progressive biliary pancreatitis (for instance, autoactivation of pancreatic enzymes, proinflammatory cytokines, oxidative stress, microcirculatory damage). In this situation a mild stress induction cannot prevent but will definitely deteriorate the inflammatory process. A previous stimulation with mediumand long-term stress induction was associated with more severe acute pancreatitis and more severe hemorrhagic ulcerations in the stomach. The au-