title: Chlorpromazine modulates cytokine expression in the liver and lung after burn injury and endotoxemia.
abstract: BACKGROUND
  Previous data from our laboratory have demonstrated that alterations in cytokine production occur in the lung and liver as the result of a two-hit model of injury, i.e., burn with subsequent endotoxin administration. The purpose of this study was to determine whether the phenothiazine derivative chlorpromazine would alter cytokine production in a sequential model of injury.
  
  
  METHODS
  By using a sublethal burn/endotoxemia model, B2D6F1 mice (n = 40) were assigned to two groups and subjected to a 15% full-thickness burn. Three days after burn injury, one group (BURN/ETX) received 2.5 mg/kg Escherichia coli endotoxin intraperitoneally, and the other group (CPZ) received 4 mg/kg chlorpromazine 1 hour before the administration of 2.5 mg/kg E. coli endotoxin intraperitoneally. At selected time points, the animals were killed and lung and liver were removed and processed for protein and total RNA. Northern blots and enzyme-linked immunosorbent assays were used to assess the production of tumor necrosis factor-alpha, macrophage inflammatory protein-1alpha, and interleukin-10.
  
  
  RESULTS
  Chlorpromazine significantly reduced tumor necrosis factor-alpha mRNA and protein expression in the liver. Macrophage inflammatory protein-1alpha mRNA was reduced by chlorpromazine in both liver and lung. Interleukin-10 production was not altered by chlorpromazine.
  
  
  CONCLUSIONS
  The reduction of tumor necrosis factor-alpha and macrophage inflammatory protein-1alpha by chlorpromazine in the liver and lungs may have potential as a pharmaceutical agent that may dampen the inflammatory response in a model of sequential injury.
authors.affiliation: Loyola University Medical Center, Department of Surgery and the Burn and Shock Trauma Institute, Maywood, Illinois 60153, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Clancy
authors.forename: K
authors.initials: K
authors.lastname: Lorenz
authors.forename: D
authors.initials: D
authors.lastname: Dries
authors.forename: R L
authors.initials: RL
authors.lastname: Gamelli
authors.forename: E L
authors.initials: EL
authors.lastname: Hahn
mesh_terms: D000818:Animals; D002056:Burns / Q000378:metabolism*; D054407:Chemokine CCL4; D002746:Chlorpromazine / Q000494:pharmacology*; D019446:Endotoxemia / Q000378:metabolism*; D004927:Escherichia coli Infections / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002746:Chlorpromazine