Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.

Endotoxin (Lipopolysaccharide, LPS) is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alv...

Full description

Bibliographic Details
Main Authors: Winfried Möller, Irene Heimbeck, Thomas P J Hofer, Gülnaz Khadem Saba, Margot Neiswirth, Marion Frankenberger, Löms Ziegler-Heitbrock
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2012-01-01
Series:PLoS ONE
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496751/?tool=EBI
_version_ 1819195319331586048
author Winfried Möller
Irene Heimbeck
Thomas P J Hofer
Gülnaz Khadem Saba
Margot Neiswirth
Marion Frankenberger
Löms Ziegler-Heitbrock
author_facet Winfried Möller
Irene Heimbeck
Thomas P J Hofer
Gülnaz Khadem Saba
Margot Neiswirth
Marion Frankenberger
Löms Ziegler-Heitbrock
author_sort Winfried Möller
collection DOAJ
description Endotoxin (Lipopolysaccharide, LPS) is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h), Interleukin-6 (peaking at 6 h), body temperature (peaking at 12 h), and CRP (peaking at 24 h). 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1)) and reactive oxygen production, assessed by hydrogen peroxide (H(2)O(2)) in fractionated exhaled breath condensate (EBC). FEV(1) showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2)O(2) induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2)O(2).Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.
first_indexed 2024-12-23T02:10:51Z
format Article
id doaj.art-2bab047863f246ca8d4745b397aae0a0
institution Directory Open Access Journal
issn 1932-6203
language English
last_indexed 2024-12-23T02:10:51Z
publishDate 2012-01-01
publisher Public Library of Science (PLoS)
record_format Article
series PLoS ONE
spelling doaj.art-2bab047863f246ca8d4745b397aae0a02022-12-21T18:03:46ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0174e3350510.1371/journal.pone.0033505Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.Winfried MöllerIrene HeimbeckThomas P J HoferGülnaz Khadem SabaMargot NeiswirthMarion FrankenbergerLöms Ziegler-HeitbrockEndotoxin (Lipopolysaccharide, LPS) is a potent inducer of inflammation and there is various LPS contamination in the environment, being a trigger of lung diseases and exacerbation. The objective of this study was to assess the time course of inflammation and the sensitivities of the airways and alveoli to targeted LPS inhalation in order to understand the role of LPS challenge in airway disease.In healthy volunteers without any bronchial hyperresponsiveness we targeted sequentially 1, 5 and 20 µg LPS to the airways and 5 µg LPS to the alveoli using controlled aerosol bolus inhalation. Inflammatory parameters were assessed during a 72 h time period. LPS deposited in the airways induced dose dependent systemic responses with increases of blood neutrophils (peaking at 6 h), Interleukin-6 (peaking at 6 h), body temperature (peaking at 12 h), and CRP (peaking at 24 h). 5 µg LPS targeted to the alveoli caused significantly stronger effects compared to 5 µg airway LPS deposition. Local responses were studied by measuring lung function (FEV(1)) and reactive oxygen production, assessed by hydrogen peroxide (H(2)O(2)) in fractionated exhaled breath condensate (EBC). FEV(1) showed a dose dependent decline, with lowest values at 12 h post LPS challenge. There was a significant 2-fold H(2)O(2) induction in airway-EBC at 2 h post LPS inhalation. Alveolar LPS targeting resulted in the induction of very low levels of EBC-H(2)O(2).Targeting LPS to the alveoli leads to stronger systemic responses compared to airway LPS targeting. Targeted LPS inhalation may provide a novel model of airway inflammation for studying the role of LPS contamination of air pollution in lung diseases, exacerbation and anti-inflammatory drugs.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496751/?tool=EBI
spellingShingle Winfried Möller
Irene Heimbeck
Thomas P J Hofer
Gülnaz Khadem Saba
Margot Neiswirth
Marion Frankenberger
Löms Ziegler-Heitbrock
Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.
PLoS ONE
title Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.
title_full Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.
title_fullStr Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.
title_full_unstemmed Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.
title_short Differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man.
title_sort differential inflammatory response to inhaled lipopolysaccharide targeted either to the airways or the alveoli in man
url https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22496751/?tool=EBI
work_keys_str_mv AT winfriedmoller differentialinflammatoryresponsetoinhaledlipopolysaccharidetargetedeithertotheairwaysorthealveoliinman
AT ireneheimbeck differentialinflammatoryresponsetoinhaledlipopolysaccharidetargetedeithertotheairwaysorthealveoliinman
AT thomaspjhofer differentialinflammatoryresponsetoinhaledlipopolysaccharidetargetedeithertotheairwaysorthealveoliinman
AT gulnazkhademsaba differentialinflammatoryresponsetoinhaledlipopolysaccharidetargetedeithertotheairwaysorthealveoliinman
AT margotneiswirth differentialinflammatoryresponsetoinhaledlipopolysaccharidetargetedeithertotheairwaysorthealveoliinman
AT marionfrankenberger differentialinflammatoryresponsetoinhaledlipopolysaccharidetargetedeithertotheairwaysorthealveoliinman
AT lomszieglerheitbrock differentialinflammatoryresponsetoinhaledlipopolysaccharidetargetedeithertotheairwaysorthealveoliinman