Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model

<p>Abstract</p> <p>Background</p> <p>Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability an...

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Main Authors: Sergi Consolato, Hager Thomas, Hauer Maria, Pilch Michael, Neumeister Johannes, Willomitzer Christian, Schmidl Elisabeth, Pircher Iris, Reinstadler Hannes, Pinna Anna, Geiger Ralf, Treml Benedikt, Schwienbacher Martin, Scholl-Bürgi Sabine, Giese Thomas, Löckinger Alexander, Nagl Markus
Format: Article
Language:English
Published: BMC 2011-08-01
Series:BMC Infectious Diseases
Online Access:http://www.biomedcentral.com/1471-2334/11/231
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author Sergi Consolato
Hager Thomas
Hauer Maria
Pilch Michael
Neumeister Johannes
Willomitzer Christian
Schmidl Elisabeth
Pircher Iris
Reinstadler Hannes
Pinna Anna
Geiger Ralf
Treml Benedikt
Schwienbacher Martin
Scholl-Bürgi Sabine
Giese Thomas
Löckinger Alexander
Nagl Markus
author_facet Sergi Consolato
Hager Thomas
Hauer Maria
Pilch Michael
Neumeister Johannes
Willomitzer Christian
Schmidl Elisabeth
Pircher Iris
Reinstadler Hannes
Pinna Anna
Geiger Ralf
Treml Benedikt
Schwienbacher Martin
Scholl-Bürgi Sabine
Giese Thomas
Löckinger Alexander
Nagl Markus
author_sort Sergi Consolato
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model.</p> <p>Methods</p> <p>Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 10<sup>8 </sup>CFU/ml <it>Streptococcus pyogenes </it>strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO<sub>2</sub>) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 10<sup>5</sup>) CFU/ml for NaCl treated pigs (p = 0.4159).</p> <p>Conclusions</p> <p>Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.</p>
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spelling doaj.art-e6b49d375e804edca391c836547ef4d32022-12-21T20:46:08ZengBMCBMC Infectious Diseases1471-23342011-08-0111123110.1186/1471-2334-11-231Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation modelSergi ConsolatoHager ThomasHauer MariaPilch MichaelNeumeister JohannesWillomitzer ChristianSchmidl ElisabethPircher IrisReinstadler HannesPinna AnnaGeiger RalfTreml BenediktSchwienbacher MartinScholl-Bürgi SabineGiese ThomasLöckinger AlexanderNagl Markus<p>Abstract</p> <p>Background</p> <p>Inhalation of N-chlorotaurine (NCT), an endogenous new broad spectrum non-antibiotic anti-infective, has been shown to be very well tolerated in the pig model recently. In the present study, inhaled NCT was tested for tolerability and efficacy in the infected bronchopulmonary system using the same model.</p> <p>Methods</p> <p>Anesthetized pigs were inoculated with 20 ml of a solution containing approximately 10<sup>8 </sup>CFU/ml <it>Streptococcus pyogenes </it>strain d68 via a duodenal tube placed through the tracheal tube down to the carina. Two hours later, 5 ml of 1% NCT aqueous solution (test group, n = 15) or 5 ml of 0.9% NaCl (control group, n = 16) was inhaled via the tracheal tube connected to a nebulizer. Inhalation was repeated every hour, four times in total. Lung function and haemodynamics were monitored. Bronchoalveolar lavage samples were removed for determination of colony forming units (CFU), and lung samples for histology.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO<sub>2</sub>) decreased rapidly after instillation of the bacteria in all animals and showed only a slight further decrease at the end of the experiment without a difference between both groups. Pulmonary artery pressure increased to a peak 1-1.5 h after application of the bacteria, decreased in the following hour and remained constant during treatment, again similarly in both groups. Histology demonstrated granulocytic infiltration in the central parts of the lung, while this was absent in the periphery. Expression of TNF-alpha, IL-8, and haemoxygenase-1 in lung biopsies was similar in both groups. CFU counts in bronchoalveolar lavage came to 170 (10; 1388) CFU/ml (median and 25 and 75 percentiles) for the NCT treated pigs, and to 250 (10; 5.5 × 10<sup>5</sup>) CFU/ml for NaCl treated pigs (p = 0.4159).</p> <p>Conclusions</p> <p>Inhaled NCT at a concentration of 1% proved to be very well tolerated also in the infected bronchopulmonary system. This study confirms the tolerability in this delicate body region, which has been proven in healthy pigs previously. Regarding efficacy, no conclusions can be drawn, mainly because of the limited test period of the model.</p>http://www.biomedcentral.com/1471-2334/11/231
spellingShingle Sergi Consolato
Hager Thomas
Hauer Maria
Pilch Michael
Neumeister Johannes
Willomitzer Christian
Schmidl Elisabeth
Pircher Iris
Reinstadler Hannes
Pinna Anna
Geiger Ralf
Treml Benedikt
Schwienbacher Martin
Scholl-Bürgi Sabine
Giese Thomas
Löckinger Alexander
Nagl Markus
Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model
BMC Infectious Diseases
title Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model
title_full Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model
title_fullStr Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model
title_full_unstemmed Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model
title_short Tolerability of inhaled N-chlorotaurine in an acute pig streptococcal lower airway inflammation model
title_sort tolerability of inhaled n chlorotaurine in an acute pig streptococcal lower airway inflammation model
url http://www.biomedcentral.com/1471-2334/11/231
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