PROJECT SUMMARY: Acute pancreatitis (AP) affects @ 275,000/ year in the USA. AP starts suddenly and unpredictably as sterile inflammation but in severe cases can get infected, resulting in sepsis, prolonged hospitalization and sometimes death. Sepsis itself affects 1.5 million people /year in the USA, costs > $20 billion, results in 12-18% mortality and has a lot in common with AP. While defined as an overwhelming response to infection, a large portion of sepsis starts in sterile diseases like AP. AP has modelled the progression of sterile diseases to infection and sepsis since sepsis was first defined in 1992. Both diseases are poorly understood, and neither has a specific targeted therapy. Both diseases, when severe have distant organ failure, which we have shown to be due to the excessive and unregulated lipolytic release of unsaturated fatty acids during AP. Unbound fatty acids (uFA) refers to the small pool (
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