Nasal PMN response to repeated challenge with endotoxin in healthy volunteers

RATIONALE: We have employed nasal challenge with lipopolysaccharide (LPS) followed by nasal lavage (NL) to experimentally induce and examine upper airway inflammation in human volunteers. It is unclear however whether adaptation within individuals occurs following repeated nasal challenge. This was...

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Main Authors: Doreswamy, Vinod, Alexis, Neil E., Zhou, Haibo, Peden, David B.
Formato: Artigo
Idioma:Inglês
Publicado em: 2011
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Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC3808958/
https://ncbi.nlm.nih.gov/pubmed/21391782
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.3109/08958378.2011.553247
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spelling pubmed-38089582013-10-28 Nasal PMN response to repeated challenge with endotoxin in healthy volunteers Doreswamy, Vinod Alexis, Neil E. Zhou, Haibo Peden, David B. Inhal Toxicol Article RATIONALE: We have employed nasal challenge with lipopolysaccharide (LPS) followed by nasal lavage (NL) to experimentally induce and examine upper airway inflammation in human volunteers. It is unclear however whether adaptation within individuals occurs following repeated nasal challenge. This was a pilot study to determine if repeated nasal LPS challenge yields attenuation of markers of inflammation (primarily neutrophil response) in the NL fluid of healthy humans. METHODS: We employed a 3-day nasal LPS challenge protocol with NL using a “split nose” design. The control and LPS nares received two consecutive day saline (0.9% saline/day) and LPS (2 μg LPS/day) challenges, respectively followed by an LPS (2 μg/day) challenge to each nare on Day 3. NL was performed immediately pre Day 1 challenges and 6-h post nasal LPS challenges on both Days 1 and 3. Markers of inflammation (PMNs/mg, cytokines) were assessed in NL and the inflammatory response to LPS (measured as the difference between pre and post challenge) was evaluated in both nares on Day 3 and compared to Day 1. RESULTS: Significant (p < 0.05) blunting of the LPS-induced polymorphonuclear leukocyte (PMN) response was observed in the nare that received repeated LPS challenges as compared to the control nare (67.60 ± 22.39 vs. 157.8 ± 76.04 PMN/mg) and initial LPS challenge on Day 1 (121 ± 32 PMN/mg). Decreased soluble CD14 and significantly decreased interleukin-8 were also found in the repeat LPS-treated nare. In the LPS-treated nare, the blunted PMN response on Day 3 correlated well with the observed PMN response on Day1 (r = 0.58, p = 0.02). CONCLUSIONS: We show attenuation of PMN response to repeated LPS in the nasal airways in healthy humans. Effect of repeat endotoxin exposure prior to allergen delivery on local airway inflammation in both healthy and atopic subjects can be studied. 2011-02 /pmc/articles/PMC3808958/ /pubmed/21391782 http://dx.doi.org/10.3109/08958378.2011.553247 Text en Copyright © 2011 Informa Healthcare USA, Inc.
institution US NLM
collection PubMed Central
language Inglês
format Artigo
topic Article
spellingShingle Article
Doreswamy, Vinod
Alexis, Neil E.
Zhou, Haibo
Peden, David B.
Nasal PMN response to repeated challenge with endotoxin in healthy volunteers
description RATIONALE: We have employed nasal challenge with lipopolysaccharide (LPS) followed by nasal lavage (NL) to experimentally induce and examine upper airway inflammation in human volunteers. It is unclear however whether adaptation within individuals occurs following repeated nasal challenge. This was a pilot study to determine if repeated nasal LPS challenge yields attenuation of markers of inflammation (primarily neutrophil response) in the NL fluid of healthy humans. METHODS: We employed a 3-day nasal LPS challenge protocol with NL using a “split nose” design. The control and LPS nares received two consecutive day saline (0.9% saline/day) and LPS (2 μg LPS/day) challenges, respectively followed by an LPS (2 μg/day) challenge to each nare on Day 3. NL was performed immediately pre Day 1 challenges and 6-h post nasal LPS challenges on both Days 1 and 3. Markers of inflammation (PMNs/mg, cytokines) were assessed in NL and the inflammatory response to LPS (measured as the difference between pre and post challenge) was evaluated in both nares on Day 3 and compared to Day 1. RESULTS: Significant (p < 0.05) blunting of the LPS-induced polymorphonuclear leukocyte (PMN) response was observed in the nare that received repeated LPS challenges as compared to the control nare (67.60 ± 22.39 vs. 157.8 ± 76.04 PMN/mg) and initial LPS challenge on Day 1 (121 ± 32 PMN/mg). Decreased soluble CD14 and significantly decreased interleukin-8 were also found in the repeat LPS-treated nare. In the LPS-treated nare, the blunted PMN response on Day 3 correlated well with the observed PMN response on Day1 (r = 0.58, p = 0.02). CONCLUSIONS: We show attenuation of PMN response to repeated LPS in the nasal airways in healthy humans. Effect of repeat endotoxin exposure prior to allergen delivery on local airway inflammation in both healthy and atopic subjects can be studied.
author Doreswamy, Vinod
Alexis, Neil E.
Zhou, Haibo
Peden, David B.
author_facet Doreswamy, Vinod
Alexis, Neil E.
Zhou, Haibo
Peden, David B.
author_sort Doreswamy, Vinod
title Nasal PMN response to repeated challenge with endotoxin in healthy volunteers
title_short Nasal PMN response to repeated challenge with endotoxin in healthy volunteers
title_full Nasal PMN response to repeated challenge with endotoxin in healthy volunteers
title_fullStr Nasal PMN response to repeated challenge with endotoxin in healthy volunteers
title_full_unstemmed Nasal PMN response to repeated challenge with endotoxin in healthy volunteers
title_sort nasal pmn response to repeated challenge with endotoxin in healthy volunteers
publishDate 2011
url https://ncbi.nlm.nih.gov/pmc/articles/PMC3808958/
https://ncbi.nlm.nih.gov/pubmed/21391782
https://ncbi.nlm.nih.govhttp://dx.doi.org/10.3109/08958378.2011.553247
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