Platelet activating factor antagonism reduces the systemic inflammatory response in a murine model of acute pancreatitis

Background. The platelet activating factor (PAF) antagonist, Lexipafant, ha s been used in experimental models and clinical trials to treat severe acut e pancreatitis (AP). The purpose of this study was to determine whether Lex ipafant reduces the local and systemic components of AP in a murine model o f mild, edematous AP. Materials and Methods. Forty-eight female SwissWebster mice were divided in to four groups. Group 1 received 50 mul of saline ip every hour for 6 h (sh am). Group 2 received saline treatment, plus Lexipafant (25 mg/kg dose ip, every 3 h starting I h after the first saline injection) (sham/Lex). Group 3 received cerulein (50 mug/kg dose ip, every hour for 6 h) (AP). Group 4 r eceived AP, plus therapeutic treatment with Lexipafant (AP/Lex). Animals we re sacrificed 3 h after the last injection. Serum cytokine levels were dete rmined by ELISA. Standard assays were performed for serum amylase activity and lung myeloperoxidase activity (MPO). Histology was scored by two blinde d investigators. Results. Serum cytokines (TNF alpha, IL-1 beta), lung MPO, and serum amylas e activity were reduced by PAF antagonism. Histology showed a trend toward improvement with Lexipafant, but did not reach statistical significance. Co nclusion. The PAF antagonism reduces the severity of systemic inflammation when given after the induction of mild AP in mice. These results suggest th at Lexipafant may be useful in the treatment of mild pancreatitis after its clinical onset. (C) 2001 Academic Press.