Platelet-activating factor and platelet-activating factor antagonists in acute pancreatitis

Introduction: Acute pancreatitis causes platelet-activating factor (PAF) to be released which induces systemic effects that contribute to circulatory disturbances and multiple organ failure, PAF has also been implicated as a key mediator in the progression of severe acute pancreatitis, which can lea d to complications and unacceptably high mortality rates. Mode of Action of PAF in Acute Pancreatitis: Synthesis of PAF is sensitive to biologically a ctive mediators seen in many inflammatory processes. PAF significantly pote ntiates pancreatic tissue damage; it causes serum amylase and lipase levels to rise significantly, causes scattered haemorrhages and may serve as a pr imary mediator of inflammation, PAF Antagonists: Several classes of compoun ds show significant PAF antagonisms, and all have shown significant local a nd systemic effects to reduce inflammatory changes. Only lexipafant, howeve r, has been studied in human acute pancreatitis. Lexipafant specifically bi nds to the PAF receptor and is more potent than other PAF antagonists. In c linical trials lexipafant reduces organ failure and suppresses some aspects of the inflammatory response. Conclusion: Our understanding of the patholo gy of systemic complications, and of a central role of PAF in mediating an inappropriate inflammatory response has improved in recent years. Confirmat ion of clinical findings with lexipafant will indicate an effective new the rapy for the treatment of severe acute pancreatitis.