dc.contributor.author | Devaney, James | |
dc.contributor.author | Curley, Gerard F | |
dc.contributor.author | Hayes, Mairead | |
dc.contributor.author | Masterson, Claire | |
dc.contributor.author | Ansari, Bilal | |
dc.contributor.author | O'Brien, Timothy | |
dc.contributor.author | O'Toole, Daniel | |
dc.contributor.author | Laffey, John G | |
dc.date.accessioned | 2018-09-20T16:05:55Z | |
dc.date.available | 2018-09-20T16:05:55Z | |
dc.date.issued | 2013-01-01 | |
dc.identifier.citation | Devaney, James; Curley, Gerard F; Hayes, Mairead; Masterson, Claire; Ansari, Bilal; O'Brien, Timothy; O'Toole, Daniel; Laffey, John G (2013). Inhibition of pulmonary nuclear factor kappa-b decreases the severity of acute escherichia coli pneumonia but worsens prolonged pneumonia. Critical Care 17 (2), | |
dc.identifier.issn | 1364-8535 | |
dc.identifier.uri | http://hdl.handle.net/10379/11171 | |
dc.description.abstract | Introduction: Nuclear factor (NF)-kappa B is central to the pathogenesis of inflammation in acute lung injury, but also to inflammation resolution and repair. We wished to determine whether overexpression of the NF-kappa B inhibitor I kappa B alpha could modulate the severity of acute and prolonged pneumonia-induced lung injury in a series of prospective randomized animal studies.
Methods: Adult male Sprague-Dawley rats were randomized to undergo intratracheal instillation of (a) 5 x 10(9) adenoassociated virus (AAV) vectors encoding the I kappa B alpha transgene (5 x 10(9) AAV-I kappa B alpha); (b) 1 x 10(10) AAV-I kappa B alpha; (c) 5 x 10(10) AAV-I kappa B alpha; or (d) vehicle alone. After intratracheal inoculation with Escherichia coli, the severity of the lung injury was measured in one series over a 4-hour period (acute pneumonia), and in a second series after 72 hours (prolonged pneumonia). Additional experiments examined the effects of I kappa B alpha and null-gene overexpression on E. coli-induced and sham pneumonia.
Results: In acute pneumonia, I kappa B alpha dose-dependently decreased lung injury, improving arterial oxygenation and lung static compliance, reducing alveolar protein leak and histologic injury, and decreasing alveolar IL-1 beta concentrations. Benefit was maximal at the intermediate (1 x 10(10)) I kappa B alpha vector dose; however, efficacy was diminished at the higher (5 x 10(10)) I kappa B alpha vector dose. In contrast, I kappa B alpha worsened prolonged pneumonia-induced lung injury, increased lung bacterial load, decreased lung compliance, and delayed resolution of the acute inflammatory response.
Conclusions: Inhibition of pulmonary NF-kappa B activity reduces early pneumonia-induced injury, but worsens injury and bacterial load during prolonged pneumonia. | |
dc.publisher | Springer Nature | |
dc.relation.ispartof | Critical Care | |
dc.rights | Attribution-NonCommercial-NoDerivs 3.0 Ireland | |
dc.rights.uri | https://creativecommons.org/licenses/by-nc-nd/3.0/ie/ | |
dc.subject | acute lung injury | |
dc.subject | inhibitory kappa-b alpha | |
dc.subject | rat | |
dc.subject | acute respiratory distress syndrome | |
dc.subject | bacteria | |
dc.subject | pneumonia | |
dc.subject | gene therapy | |
dc.subject | acute lung injury | |
dc.subject | respiratory-distress-syndrome | |
dc.subject | hypercapnic acidosis | |
dc.subject | bacterial pneumonia | |
dc.subject | risk-factors | |
dc.subject | induced inflammation | |
dc.subject | activation | |
dc.subject | sepsis | |
dc.subject | rats | |
dc.subject | mice | |
dc.title | Inhibition of pulmonary nuclear factor kappa-b decreases the severity of acute escherichia coli pneumonia but worsens prolonged pneumonia | |
dc.type | Article | |
dc.identifier.doi | 10.1186/cc12696 | |
dc.local.publishedsource | https://ccforum.biomedcentral.com/track/pdf/10.1186/cc12696?site=ccforum.biomedcentral.com | |
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