Platelet-activating factor and platelet-activating factor antagonists in acute pancreatitis.
BACKGROUND
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 lead to complications and unacceptably high mortality rates.
Synthesis of PAF is sensitive to biologically active mediators seen in many inflammatory processes. PAF significantly potentiates pancreatic tissue damage; it causes serum amylase and lipase levels to rise significantly, causes scattered haemorrhages and may serve as a primary mediator of inflammation.
Several classes of compounds show significant PAF antagonisms, and all have shown significant local and systemic effects to reduce inflammatory changes. Only lexipafant, however, has been studied in human acute pancreatitis. Lexipafant specifically binds to the PAF receptor and is more potent than other PAF antagonists. In clinical trials lexipafant reduces organ failure and suppresses some aspects of the inflammatory response.


CONCLUSIONS
Our understanding of the pathology of systemic complications, and of a central role of PAF in mediating an inappropriate inflammatory response has improved in recent years. Confirmation of clinical findings with lexipafant will indicate an effective new therapy for the treatment of severe acute pancreatitis.
Johnson
C D
CD
University Surgical Unit, Southampton General Hospital, Southampton, UK. c.d.johnson@soton.ac.uk
D000208:Acute Disease; D000818:Animals; D018450:Disease Progression; D006801:Humans; D010195:Pancreatitis / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D010972:Platelet Activating Factor / Q000032:analysis / Q000096:biosynthesis*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011379:Prognosis; D051381:Rats; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D010972:Platelet Activating Factor; D010975:Platelet Aggregation Inhibitors