Analysis of trigger mechanisms for inflammation in cardiovascular disease:: Application to shock and multiorgan failure

Cell activation in the microcirculation and inflammatory mediators have become a central focus of research into many cardiovascular diseases. However, the possible trigger mechanisms of inflammation remain less well understood. We summarize here a series of studies designed to investigate the origin of inflammation in acute physiological shock, a potentially lethal condition. A series of basic studies demonstrated that a major source of the inflammatory mediators in shock, produced in an ischemic intestine or after endotoxin administration, is due to the action of digestive enzymes. Many of these enzymes are proteases derived from the pancreas. The proteolytic and lipolytic action of pancreatic enzymes leads to the release of inflammatory mediators from the wall of the intestine. These mediators are transported via the intestinal microcirculation and the lymphatics into the central circulation, where they can initiate an inflammatory cascade with eventual multi-organ failure. These observations offer an opportunity for testing novel interventions against the lethal outcome of shock.