PMID- 25377849
OWN - NLM
STAT- MEDLINE
DCOM- 20160202
LR  - 20181113
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 79
IP  - 5
DP  - 2015 May
TI  - Characterization of the inflammatory response to inhaled lipopolysaccharide in 
      mild to moderate chronic obstructive pulmonary disease.
PG  - 767-76
LID - 10.1111/bcp.12546 [doi]
AB  - AIMS: Lipopolysaccharide (LPS) inhalation causes increased airway and systemic 
      inflammation. We investigated LPS inhalation in patients with chronic obstructive 
      pulmonary disease (COPD) as a model of bacterial exacerbations. We studied 
      safety, changes in sputum and systemic biomarkers. We have also investigated 
      interleukin (IL)-17 concentrations in this model. METHODS: Twelve COPD patients 
      inhaled 5 mug LPS. Safety was monitored over 24 h. Sputum was induced at baseline, 
      6 and 24 h for cells and IL-8, IL-17, neutrophil elastase, monocyte 
      chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1beta (MIP-1beta) 
      in supernatants. Serum was collected at baseline, 4, 8 and 24 h for IL-6, 
      C-reactive protein (CRP) and Clara cell protein (CC-16) concentrations. 
      Peripheral blood mononuclear cells (PBMCs) were isolated at baseline and 4 h for 
      systemic IL-17 analysis. RESULTS: LPS 5 mug was well tolerated. The greatest FEV1 
      change was 11.7% (mean) at 1 h (95% CI 5.1-18.2%). There was a large range in 
      maximal fall (2.5-37.7%). Total sputum cell count and neutrophil count 
      significantly increased 6 and 24 h post-LPS. There was no change in sputum 
      supernatant mediators. IL-6, CRP and CC-16 increased post-inhalation, with 
      different temporal patterns. CD4+ and CD8+ cell associated IL-17 significantly 
      increased at 4 h. CONCLUSIONS: Inhaled LPS in COPD patients safely causes 
      increased airway and systemic inflammation. This may be a model for studying COPD 
      exacerbations.
CI  - (c) 2014 The British Pharmacological Society.
FAU - Gupta, Vandana
AU  - Gupta V
AD  - Medicines Evaluation Unit, University Hospital of South Manchester Foundation 
      Trust, University of Manchester, Southmoor Rd, Manchester, UK.
FAU - Banyard, Antonia
AU  - Banyard A
FAU - Mullan, Aoibheann
AU  - Mullan A
FAU - Sriskantharajah, Srividya
AU  - Sriskantharajah S
FAU - Southworth, Thomas
AU  - Southworth T
FAU - Singh, Dave
AU  - Singh D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Adrenal Cortex Hormones)
RN  - 0 (Biomarkers)
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Adrenal Cortex Hormones/administration & dosage/therapeutic use
MH  - Biomarkers/analysis/blood
MH  - Cell Count
MH  - Disease Progression
MH  - Female
MH  - Flow Cytometry
MH  - Humans
MH  - *Inhalation Exposure/adverse effects
MH  - Lipopolysaccharides/administration & dosage/*immunology
MH  - Lymphocytes/drug effects/immunology
MH  - Male
MH  - Middle Aged
MH  - Pulmonary Disease, Chronic Obstructive/blood/drug therapy/*immunology
MH  - Severity of Illness Index
MH  - Sputum/cytology/immunology
PMC - PMC4415713
OTO - NOTNLM
OT  - COPD
OT  - COPD exacerbations
OT  - IL-17
OT  - lipopolysaccharide
OT  - sputum neutrophils
EDAT- 2014/11/08 06:00
MHDA- 2016/02/03 06:00
PMCR- 2016/05/01
CRDT- 2014/11/08 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/10/28 00:00 [accepted]
PHST- 2014/11/08 06:00 [entrez]
PHST- 2014/11/08 06:00 [pubmed]
PHST- 2016/02/03 06:00 [medline]
PHST- 2016/05/01 00:00 [pmc-release]
AID - 10.1111/bcp.12546 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2015 May;79(5):767-76. doi: 10.1111/bcp.12546.