Document Detail

A randomized controlled trial of peripheral blood mononuclear cell depletion in experimental human lung inflammation.
MedLine Citation:
PMID:  23627345     Owner:  NLM     Status:  MEDLINE    
RATIONALE: Depletion of monocytes reduces LPS-induced lung inflammation in mice, suggesting monocytes as potential therapeutic targets in acute lung injury.
OBJECTIVES: 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.
MEASUREMENTS AND MAIN 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.
Laura C Barr; Mairi Brittan; Andrew Conway Morris; Daniel F McAuley; Chiara McCormack; Alison M Fletcher; Hamish Richardson; Martin Connell; Dilip Patel; William A H Wallace; Adriano G Rossi; Donald J Davidson; Lynn Manson; Marc Turner; Nikhil Hirani; Timothy S Walsh; Niall H Anderson; Kevin Dhaliwal; A John Simpson
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Publication Detail:
Type:  Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  American journal of respiratory and critical care medicine     Volume:  188     ISSN:  1535-4970     ISO Abbreviation:  Am. J. Respir. Crit. Care Med.     Publication Date:  2013 Aug 
Date Detail:
Created Date:  2013-08-16     Completed Date:  2014-02-04     Revised Date:  2014-03-31    
Medline Journal Info:
Nlm Unique ID:  9421642     Medline TA:  Am J Respir Crit Care Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  449-55     Citation Subset:  AIM; IM    
Data Bank Information
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MeSH Terms
Bronchoalveolar Lavage
Cytokines / blood
Double-Blind Method
Inflammation Mediators / physiology*
Leukocytes, Mononuclear
Up-Regulation / physiology
Young Adult
Grant Support
G0601401//Medical Research Council; G0701690//Medical Research Council; G0901697//Medical Research Council; G1002046//Medical Research Council; MR/J014702/1//Medical Research Council
Reg. No./Substance:
0/Cytokines; 0/Inflammation Mediators
Comment In:
Am J Respir Crit Care Med. 2014 Feb 15;189(4):499-500   [PMID:  24528324 ]
Am J Respir Crit Care Med. 2013 Aug 15;188(4):407-8   [PMID:  23947514 ]
Am J Respir Crit Care Med. 2014 Feb 15;189(4):500-1   [PMID:  24528325 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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