Platelet-activating factor.

Abstract

Platelet-activating factor (PAF) is a proinflammatory lipid. It has been strongly implicated in the regulation of pancreatic exocrine secretion and in the local and systemic events which occur in acute pancreatitis. PAF antagonists, when given as pretreatment, ameliorate the severity of experimental acute pancreatitis by reducing serum amylase, oxidative injury, morphological changes, polymorph infiltration, pulmonary damage, and exudative levels of PAF in blood and peritoneal fluid. The novel, potent PAF antagonist, lexipafant, can ameliorate microvascular-induced acute pancreatitis after induction of the disease. It also reduces lung injury by preventing increased pulmonary capillary permeability. In a double-blind, randomized, Phase II, clinical study of lexipafant in human acute pancreatitis, a clinical benefit was found, as indicated by a significant reduction in an organ failure score measured during 72 h of infusion. In addition, organ failure recovered in seven of 12 severe acute pancreatitis patients treated with lexipafant, but recovered in only two of 11 patients given placebo. New organ failure developed in a further two patients on placebo. The results of these studies indicate that lexipafant is a potential therapy for the treatment of human acute pancreatitis. A multicentre, Phase III, UK study in patients with severe acute pancreatitis is currently underway.