Acute Lung Injury in Response to Intratracheal Instillation of Lipopolysaccharide in an Animal Model of Emphysema Induced by Elastase.

Abstract

The response of lungs with emphysema to an acute lung injury (ALI) remains unclear. This study compared the lung response to intratracheal instillation of lipopolysaccharide (LPS) in rats with and without emphysema. Twenty-four Wistar rats were randomized to four groups: control group (C-G), ALI group (ALI-G), emphysema group (E-G), emphysema and ALI group (E-ALI-G). Euthanasia and the following analysis were performed 24h after ALI induction: lung histology, bronchoalveolar lavage (BAL), mRNA expression of inflammatory mediators, and blood gas measures. The histological analysis showed that animals of ALI-G (0.55±0.15) and E-ALI-G (0.69±0.08) had a higher ALI score compared to C-G (0.12±0.04) and E-G (0.16±0.04) (p<0.05). The analysis of each component of the score demonstrated that ALI-G and E-ALI-G had greater alveolar and interstitial neutrophil infiltration, as well as greater amount of alveolar proteinaceous debris. Comparing the two groups that received LPS, there was a trend of higher ALI in the E-ALI-G, specially due to a higher neutrophil infiltration in the alveolar spaces and a higher septal thickening. Total cell count (E-G=3.09±0.83; ALI-G=4.45±1.9; E-ALI-G=5.9±2.1; C-G=0.73±0.37×105) and neutrophil count (E-G=0.69±0.35; ALI-G=2.53±1.09; E-ALI-G=3.86±1.4; C-G=0.09±0.07×105) in the BAL were higher in the groups E-G, ALI-G, and E-ALI-G when compared to C-G (p<0.05). The IL-6, TNF-α, and CXCL2 mRNA expressions were higher in the animals that received LPS (ALI-G and E-ALI-G) compared to the C-G and E-G (p<0.05). No statistically significant difference was observed in the BAL cellularity and in the expression of inflammatory mediators between the ALI-G and the E-ALI-G. The severity of ALI in response to intratracheal instillation of LPS did not show difference in rats with and without intratracheal-induced emphysema.