title: Treatment with Evasin-3 abrogates neutrophil-mediated inflammation in mouse acute pancreatitis.
abstract: BACKGROUND
  Acute pancreatitis is characterized by inflammatory processes affecting not only the pancreas, but also the lung. Here, we investigated timing of leucocyte infiltration and chemokine expression within lung and pancreas during pancreatitis and whether treatments selectively inhibiting chemokines (using Evasins) could improve organ injury.
  
  
  METHODS
  C57Bl/6 mice were submitted in vivo to 10-h intraperitoneal injections of cerulein and followed for up to 168 h. Five minutes after the first cerulein injection, a single intraperitoneal injection of 10 μg Evasin-3, 1 μg Evasin-4 or an equal volume of vehicle (PBS) was performed. Leucocytes, reactive oxygen species (ROS), necrosis and chemokine/cytokine mRNA expression were assessed in different organs by immunohistology and real-time RT-PCR, respectively.
  
  
  RESULTS
  In the lung, neutrophil infiltration and macrophage infiltration peaked at 12 h and were accompanied by increased CXCL2 mRNA expression. CCL2, CXCL1 and TNF-alpha significantly increased after 24 h as compared to baseline. No increase in CCL3 and CCL5 was observed. In the pancreas, neutrophil infiltration peaked at 6 h, while macrophages increased only after 72 h. Treatment with Evasin-3 decreased neutrophil infiltration, ROS production and apoptosis in the lung and reduced neutrophils, macrophages apoptosis and necrosis in the pancreas. Evasin-4 only reduced macrophage content in the lung and did not provide any benefit at the pancreas level.
  
  
  CONCLUSIONS
  Chemokine production and leucocyte infiltration are timely regulated in lung and pancreas during pancreatitis. CXC chemokine inhibition with Evasin-3 improved neutrophil inflammation and injury, potentially interfering with damages in acute pancreatitis and related pulmonary complications.
authors.affiliation: Division of Cardiology, Foundation for Medical Researches, University of Geneva, Geneva, Switzerland; First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa School of Medicine, IRCCS Azienda Ospedaliera Universitaria San Martino-IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; Division of Laboratory Medicine, Department of Genetics and Laboratory Medicine, Geneva University Hospitals, Geneva, Switzerland.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Montecucco
authors.forename: François
authors.initials: F
authors.lastname: Mach
authors.forename: Sébastien
authors.initials: S
authors.lastname: Lenglet
authors.forename: Alain
authors.initials: A
authors.lastname: Vonlaufen
authors.forename: Ana Luíza
authors.initials: AL
authors.lastname: Gomes Quinderé
authors.forename: Graziano
authors.initials: G
authors.lastname: Pelli
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burger
authors.forename: Katia
authors.initials: K
authors.lastname: Galan
authors.forename: Franco
authors.initials: F
authors.lastname: Dallegri
authors.forename: Federico
authors.initials: F
authors.lastname: Carbone
authors.forename: Amanda E
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vuilleumier
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Frossard
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D060829:Arthropod Proteins; D002108:Ceruletide / Q000633:toxicity; D054360:Chemokine CXCL1 / Q000037:antagonists & inhibitors; D054426:Chemokine CXCL2 / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D009336:Necrosis; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy*; D017382:Reactive Oxygen Species / Q000378:metabolism; D054387:Receptors, CXCR / Q000627:therapeutic use*; D012471:Salivary Proteins and Peptides
chemical_list: D000893:Anti-Inflammatory Agents; D060829:Arthropod Proteins; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; C550668:Evasin-3 protein, tick; D017382:Reactive Oxygen Species; D054387:Receptors, CXCR; D012471:Salivary Proteins and Peptides; D002108:Ceruletide
keywords: Inflammation; lung; pancreas; pancreatic damage; pancreatitis