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

Abstract

OBJECTIVES:

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: Stephen Thacker, Ana Moran, Mihalis Lionakis, Mary-Ann A Mastrangelo, Tripti Halder, Maria del Pilar Huby, Yong Wu, David J Tweardy
• Journal: The Journal of infection (J Infect) Vol. 68 Issue 3 Pg. 231-41 (Mar 2014) ISSN: 1532-2742 [Electronic] England
• PMID: 24291043 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Chemical References

• Interleukin-6
• Pulmonary Surfactant-Associated Protein D

Topics

• Analysis of Variance
• Animals
• Apoptosis (physiology)
• Disease Models, Animal
• Interleukin-6 (administration & dosage, pharmacology)
• Pneumonia (prevention & control)
• Pulmonary Surfactant-Associated Protein D (metabolism)
• Rats
• Shock, Hemorrhagic (physiopathology)
• Unfolded Protein Response (drug effects, physiology)