title: Glucocorticoid receptor blockade reverses postinjury macrophage suppression.
abstract: OBJECTIVE
  To study the effects of the stress-induced surge of endogenous glucocorticoids on macrophage function and the role of inhibiting glucocorticoids with a receptor antagonist, mifepristone (RU 486).
  
  
  METHODS
  One hundred thirty female Swiss-Webster mice were randomly assigned to either injury by femur fracture or uninjured anesthesia control in this intervention study.
  
  
  METHODS
  A university-based surgical laboratory and animal facility.
  
  
  METHODS
  Injured mice were randomized to receive either the glucocorticoid receptor antagonist mifepristone (10 mg/kg by oral gavage) or its vehicle. Mifepristone or its vehicle were given either 2 hours before or 2 hours after the injury.
  
  
  METHODS
  Peritoneal macrophages were harvested 24 hours after the injury. Macrophages were assayed for the stimulated (phorbol myristate acetate, 1 microgram/mL) production of superoxide anion, secretion of interleukin-6, tumor necrosis factor alpha, and prostaglandin E2 in response to endotoxin (lipopolysaccharide at 10 micrograms/mL) and killing of Candida albicans.
  
  
  RESULTS
  Pretreatment with mifepristone significantly prevented or reduced suppression of several macrophage functions following injury, including superoxide production and C albicans killing. Treatment after the injury preserved only C albicans. Mifepristone failed to block the increased secretion of prostaglandin E2 after injury.
  
  
  CONCLUSIONS
  Pretreatment with mifepristone before an injury prevented suppression of several macrophage functions. Further studies are required on the effects of glucocorticoid inhibition on other aspects of the immune and metabolic responses to injury to define the potential clinical applications of mifepristone trauma.
authors.affiliation: Harrison Department of Surgical Research, University of Pennsylvania School of Medicine, Pittsburgh.
authors.forename: A C
authors.initials: AC
authors.lastname: Cech
authors.forename: J
authors.initials: J
authors.lastname: Shou
authors.forename: H
authors.initials: H
authors.lastname: Gallagher
authors.forename: J M
authors.initials: JM
authors.lastname: Daly
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015232:Dinoprostone / Q000032:analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D005264:Femoral Fractures / Q000188:drug therapy* / Q000276:immunology*; D015850:Interleukin-6 / Q000032:analysis; D008262:Macrophage Activation / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000737:chemistry / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D015735:Mifepristone / Q000494:pharmacology*; D011292:Premedication; D011897:Random Allocation; D011965:Receptors, Glucocorticoid / Q000187:drug effects*; D013312:Stress, Physiological / Q000188:drug therapy / Q000276:immunology; D013481:Superoxides / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D015850:Interleukin-6; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015735:Mifepristone; D015232:Dinoprostone