title: Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans.
abstract: OBJECTIVE
  The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute-phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti-inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin.
  
  
  METHODS
  In this randomized, double-blind and placebo-controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage.
  
  
  RESULTS
  Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C-reactive protein release. In sharp contrast, dexamethasone left the local release of acute-phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL-6 were only 18% lower and levels of IL-8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration.
  
  
  CONCLUSIONS
  The present study demonstrated a remarkable dissociation between the systemic anti-inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti-inflammatory effects in the lungs on the other.
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Johann
authors.initials: J
authors.lastname: Bartko
authors.affiliation: Department of Pulmonology, Medical University of Vienna, Vienna, Austria.
authors.forename: Leopold
authors.initials: L
authors.lastname: Stiebellehner
authors.affiliation: Department of Emergency Medicine, Medical University of Vienna, Vienna, Austria.
authors.forename: Ulla
authors.initials: U
authors.lastname: Derhaschnig
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Schoergenhofer
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Schwameis
authors.affiliation: Department of Radiology, Medical University of Vienna, Vienna, Austria.
authors.forename: Helmut
authors.initials: H
authors.lastname: Prosch
authors.affiliation: Department of Clinical Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
mesh_terms: D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid; D002097:C-Reactive Protein / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D004731:Endotoxins / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology* / Q000627:therapeutic use; D064368:Healthy Volunteers; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis* / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D016209:Interleukin-8 / Q000032:analysis / Q000378:metabolism; D008297:Male; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; D004731:Endotoxins; D005938:Glucocorticoids; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D003907:Dexamethasone; D002097:C-Reactive Protein
keywords: acute respiratory distress syndrome; dexamethasone; lipopolysaccharide; lung inflammation; surfactant protein D