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Restoration of lung surfactant protein D by IL-6 protects against secondary pneumonia following hemorrhagic shock

Authors
  • Thacker, Stephen
  • Moran, Ana
  • Lionakis, Mihalis
  • Mastrangelo, Mary-Ann A.
  • Halder, Tripti
  • Huby, Maria del Pilar
  • Wu, Yong
  • Tweardy, David J.1, 2, 3, 1, 4, 3, 5, 3, 6, 3
  • 1 Section of Infectious Diseases
  • 2 Department of Pediatrics
  • 3 Baylor College of Medicine
  • 4 Department of Medicine
  • 5 Department of Molecular and Cellular Biology
  • 6 Department of Biochemistry and Molecular Biology
Type
Published Article
Journal
Journal of Infection
Publisher
Elsevier
Publication Date
Jan 01, 2013
Accepted Date
Nov 19, 2013
Volume
68
Issue
3
Pages
231–241
Identifiers
DOI: 10.1016/j.jinf.2013.11.010
Source
Elsevier
Keywords
License
Unknown

Abstract

ObjectivesTo identify novel approaches to improve innate immunity in the lung following trauma complicated by hemorrhagic shock (T/HS) for prevention of nosocomial pneumonia. MethodsWe developed a rat model of T/HS followed by Pseudomonas aeruginosa (PA) pneumonia to assess the effect of alveolar epithelial cell (AEC) apoptosis, and its prevention by IL-6, on lung surfactant protein (SP)-D protein levels, lung bacterial burden, and survival from PA pneumonia, as well as to determine whether AEC apoptosis is a consequence of the unfolded protein response (UPR). Lung UPR transcriptome analysis was performed on rats subjected to sham, T/HS, and T/HS plus IL-6 protocols. Group comparisons were performed via Kaplan–Meier or ANOVA. ResultsT/HS decreased lung SP-D by 1.8-fold (p < 0.05), increased PA bacterial burden 9-fold (p < 0.05), and increased PA pneumonia mortality by 80% (p < 0.001). IL-6, when provided at resuscitation, normalized SP-D levels (p < 0.05), decreased PA bacterial burden by 4.8-fold (p < 0.05), and prevented all mortality from PA pneumonia (p < 0.001). The UPR transcriptome was significantly impacted by T/HS; IL-6 treatment normalized the T/HS-induced UPR transcriptome changes (p < 0.05). ConclusionsImpaired innate lung defense occurs following T/HS and is mediated, in part, by reduction in SP-D protein levels, which, along with AEC apoptosis, may be mediated by the UPR, and prevented by use of IL-6 as a resuscitation adjuvant.

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