title: Therapeutic administration of orlistat, rosiglitazone, or the chemokine receptor antagonist RS102895 fails to improve the severity of acute pancreatitis in obese mice.
abstract: OBJECTIVE
  Currently, there is no therapy for severe acute pancreatitis (AP) except for supportive care. The lipase inhibitor orlistat, the peroxisome proliferator-activated receptor γ agonist rosiglitazone, and the chemokine receptor 2 antagonists attenuate the severity of AP in rodents if administered before or at the time of induction of pancreatitis. However, it is unknown whether these treatments are effective if administered therapeutically after induction of pancreatitis.
  
  
  METHODS
  Male C57BL6 mice with diet-induced obesity received 2 injections of mrIL-12 (150 ng per mouse) and mrIL-18 (750 ng per mouse) intraperitoneally at 24-hour intervals. The mice were injected 2, 24, and 48 hours after the second injection of IL-12 + IL-18 with orlistat (2 mg per mouse), rosiglitazone (0.4 mg per mouse), RS102895 (0.3 mg per mouse), or vehicle (20 μL of DMSO and 80 μL of canola oil) and euthanized after 72 hours.
  
  
  RESULTS
  Orlistat decreased intra-abdominal fat necrosis compared with vehicle (P < 0.05). However, none of the drug treatments produced significant decreases in pancreatic edema, acinar necrosis, or intrapancreatic fat necrosis.
  
  
  CONCLUSIONS
  Drugs previously shown to improve the severity of AP when given before or at the time of induction of pancreatitis failed to do so when administered therapeutically in the IL-12 + IL-18 model.
authors.affiliation: From the Departments of *Medicine, †Kinesiology and Nutrition, and ‡Pathology, University of Illinois at Chicago, Chicago, IL.
authors.forename: Elise A
authors.initials: EA
authors.lastname: Malecki
authors.forename: Karla J
authors.initials: KJ
authors.lastname: Castellanos
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Cabay
authors.forename: Giamila
authors.initials: G
authors.lastname: Fantuzzi
mesh_terms: D000208:Acute Disease; D000818:Animals; D019440:Anti-Obesity Agents / Q000008:administration & dosage / Q000494:pharmacology; D048588:Benzoxazines / Q000008:administration & dosage / Q000494:pharmacology*; D018664:Interleukin-12; D020382:Interleukin-18; D007783:Lactones / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy*; D000077403:Orlistat; D010195:Pancreatitis / Q000139:chemically induced / Q000188:drug therapy*; D010880:Piperidines / Q000008:administration & dosage / Q000494:pharmacology*; D054390:Receptors, CCR2 / Q000037:antagonists & inhibitors; D000077154:Rosiglitazone; D012720:Severity of Illness Index; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000494:pharmacology*; D017211:Treatment Failure; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D019440:Anti-Obesity Agents; D048588:Benzoxazines; D020382:Interleukin-18; D007783:Lactones; D010880:Piperidines; C573791:RS 102895; D054390:Receptors, CCR2; D045162:Thiazolidinediones; D014665:Vasodilator Agents; D000077154:Rosiglitazone; D018664:Interleukin-12; D000077403:Orlistat