title: A randomized controlled trial of peripheral blood mononuclear cell depletion in experimental human lung inflammation.
abstract: BACKGROUND
  Depletion of monocytes reduces LPS-induced lung inflammation in mice, suggesting monocytes as potential therapeutic targets in acute lung injury.
  
  
  OBJECTIVE
  To investigate whether depletion of circulating blood monocytes has beneficial effects on markers of systemic and pulmonary inflammation in a human model of acute lung inflammation.
  
  
  METHODS
  A total of 30 healthy volunteers were enrolled in a randomized controlled trial. Volunteers inhaled LPS at baseline, and were randomized to receive active mononuclear cell depletion by leukapheresis, or sham leukapheresis, in a double-blind fashion (15 volunteers per group). Serial blood counts were measured, bronchoalveolar lavage (BAL) was performed at 9 hours, and [(18)F]fluorodeoxyglucose positron emission tomography at 24 hours. The primary endpoint was the increment in circulating neutrophils at 8 hours.
  
  
  RESULTS
  As expected, inhalation of LPS induced neutrophilia and an up-regulation of inflammatory mediators in the blood and lungs of all volunteers. There was no significant difference between the depletion and sham groups in the mean increment in blood neutrophil count at 8 hours (6.16 × 10(9)/L and 6.15 × 10(9)/L, respectively; P = 1.00). Furthermore, there were no significant differences in BAL neutrophils or protein, positron emission tomography-derived measures of global lung inflammation, or cytokine levels in plasma or BAL supernatant between the study groups. No serious adverse events occurred, and no symptoms were significantly different between the groups.
  
  
  CONCLUSIONS
  These findings do not support a role for circulating human monocytes in the early recruitment of neutrophils during LPS-mediated acute lung inflammation in humans.
authors.affiliation: University of Edinburgh/Medical Research Council Centre for Inflammation Research, Queen's Medical Research Institute, Edinburgh, United Kingdom.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Barr
authors.forename: Mairi
authors.initials: M
authors.lastname: Brittan
authors.forename: Andrew Conway
authors.initials: AC
authors.lastname: Morris
authors.forename: Daniel F
authors.initials: DF
authors.lastname: McAuley
authors.forename: Chiara
authors.initials: C
authors.lastname: McCormack
authors.forename: Alison M
authors.initials: AM
authors.lastname: Fletcher
authors.forename: Hamish
authors.initials: H
authors.lastname: Richardson
authors.forename: Martin
authors.initials: M
authors.lastname: Connell
authors.forename: Dilip
authors.initials: D
authors.lastname: Patel
authors.forename: William A H
authors.initials: WA
authors.lastname: Wallace
authors.forename: Adriano G
authors.initials: AG
authors.lastname: Rossi
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Davidson
authors.forename: Lynn
authors.initials: L
authors.lastname: Manson
authors.forename: Marc
authors.initials: M
authors.lastname: Turner
authors.forename: Nikhil
authors.initials: N
authors.lastname: Hirani
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Walsh
authors.forename: Niall H
authors.initials: NH
authors.lastname: Anderson
authors.forename: Kevin
authors.initials: K
authors.lastname: Dhaliwal
authors.forename: A John
authors.initials: AJ
authors.lastname: Simpson
mesh_terms: D000293:Adolescent; D000328:Adult; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000097:blood; D004311:Double-Blind Method; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D007937:Leukapheresis; D007963:Leukocytes, Mononuclear; D008297:Male; D015854:Up-Regulation / Q000502:physiology; D055815:Young Adult
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators