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

Abstract

To identify novel approaches to improve innate immunity in the lung following trauma complicated by hemorrhagic shock (T/HS) for prevention of nosocomial pneumonia. 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. 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). 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.