title: Restoration of lung surfactant protein D by IL-6 protects against secondary pneumonia following hemorrhagic shock.
abstract: OBJECTIVE
  To identify novel approaches to improve innate immunity in the lung following trauma complicated by hemorrhagic shock (T/HS) for prevention of nosocomial pneumonia.
  
  
  METHODS
  We 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.
  
  
  RESULTS
  T/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).
  
  
  CONCLUSIONS
  Impaired 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.
authors.affiliation: Section of Infectious Diseases, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Thacker
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Moran
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Mihalis
authors.initials: M
authors.lastname: Lionakis
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Mary-Ann A
authors.initials: MA
authors.lastname: Mastrangelo
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Tripti
authors.initials: T
authors.lastname: Halder
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: del Pilar Huby
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Section of Infectious Diseases, Department of Medicine, Baylor College of Medicine, Houston, TX, USA; Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, TX, USA. Electronic address: dtweardy@bcm.edu.
authors.forename: David J
authors.initials: DJ
authors.lastname: Tweardy
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004195:Disease Models, Animal; D015850:Interleukin-6 / Q000008:administration & dosage / Q000494:pharmacology*; D011014:Pneumonia / Q000517:prevention & control*; D037663:Pulmonary Surfactant-Associated Protein D / Q000378:metabolism*; D051381:Rats; D012771:Shock, Hemorrhagic / Q000503:physiopathology*; D056811:Unfolded Protein Response / Q000187:drug effects / Q000502:physiology
chemical_list: D015850:Interleukin-6; D037663:Pulmonary Surfactant-Associated Protein D
keywords: Alveolar epithelial cell; Hemorrhagic shock; Pneumonia; Unfolded protein response