The effect of lexipafant on bacterial translocation in acute necrotizing pancreatitis in rats

Bacterial translocation (BT) from the gastrointestinal tract to mesenteric lymph nodes (MLNs) and other extra intestinal organs is an important source of infection in acute pancreatitis (AP). Lexipafant (BB-882) is a potent p latelet-activating factor receptor antagonist that has an anti-inflammatory effect. To examine whether BB-882 could affect BT in acute necrotizing pan creatitis, 48 male Sprague Dawley rats (250-350 g) were studied. AP was ind uced in Group I and Group II by pressure injection of 3% taurocholate and t rypsin into the common biliopancreatic duct (1 mL/kg of body weight). Group I rats received BB-882 (10 mg/kg, ip qd) and Group II rats received a simi lar volume of normal saline as a placebo postoperatively for 2 days. Group III and Group TV received BB-882 and placebo, respectively, after an explor atory laparotomy. At 48 hours postoperatively, blood was drawn for culture, serum amylase, and tumor necrosis factor (TNF)-alpha determinations. Speci mens from MLNs, spleen, liver, pancreas, and cecum were harvested for cultu re of Gram-positive, Gram-negative, and anaerobic bacteria. Quantitative ce cal cultures of Gram-positive, Gram-negative, and anaerobic bacteria were o btained. A point scoring system for five histological features that include interstitial edema, inflammatory cellular infiltration, fat necrosis, pare nchymal necrosis, and hemorrhage was used to evaluate the severity of pancr eatitis. There was no difference in serum amylase levels (2415 +/- 127 IU/L versus 2476 +/- 170 IU/L), serum TNF-alpha levels (7820 +/- 1396 pg/mL ver sus 7318 +/- 681 pg/mL), and the mean pancreatic histology score (5.9 +/- 1 .2 versus 6.5 +/- 1.1) between Group I and Group II, respectively (P > 0.05 ). Seven of 12 Group I rats had BT to MLNs, compared with 11 of 12 rats in Group II (P > 0.05). Five of 12 Group I rats had BT to distant sites such a s pancreas, spleen, liver, and/or blood, compared with II of 12 rats in Gro up II (P < 0.05). BB-882 treatment decreases bacterial spread to distant si tes, but does not reduce serum amylase levels and serum TNF-alpha levels or ameliorate pancreatic damage in rats with AP.