Show simple item record

dc.contributor.authorDevaney, James
dc.contributor.authorCurley, Gerard F
dc.contributor.authorHayes, Mairead
dc.contributor.authorMasterson, Claire
dc.contributor.authorAnsari, Bilal
dc.contributor.authorO'Brien, Timothy
dc.contributor.authorO'Toole, Daniel
dc.contributor.authorLaffey, John G
dc.identifier.citationDevaney, 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.description.abstractIntroduction: 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.publisherSpringer Nature
dc.relation.ispartofCritical Care
dc.rightsAttribution-NonCommercial-NoDerivs 3.0 Ireland
dc.subjectacute lung injury
dc.subjectinhibitory kappa-b alpha
dc.subjectacute respiratory distress syndrome
dc.subjectgene therapy
dc.subjectacute lung injury
dc.subjecthypercapnic acidosis
dc.subjectbacterial pneumonia
dc.subjectinduced inflammation
dc.titleInhibition of pulmonary nuclear factor kappa-b decreases the severity of acute escherichia coli pneumonia but worsens prolonged pneumonia

Files in this item


This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivs 3.0 Ireland
Except where otherwise noted, this item's license is described as Attribution-NonCommercial-NoDerivs 3.0 Ireland