Effects of Obesity on Pulmonary Inflammation and Remodeling in Experimental Moderate Acute Lung Injury.

Lígia De A Maia,Paolo Pelosi,Cynthia S Samary,Fernanda F Cruz,Stefano De A A Trivelin,Pedro L Silva,Marcelo Gama De Abreu,Nazareth De N Rocha,Marcos Vinicius De S Fernandes,Milena V De Oliveira,Patricia R M Rocco

doi:10.3389/fimmu.2019.01215

Abstract

Obese patients are at higher risk of developing acute respiratory distress syndrome (ARDS); however, their survival rates are also higher compared to those of similarly ill non-obese patients. We hypothesized that obesity would not only prevent lung inflammation, but also reduce remodeling in moderate endotoxin-induced acute lung injury (ALI). Obesity was induced by early postnatal overfeeding in Wistar rats in which the litter size was reduced to 3 pups/litter (Obese, n = 18); Control animals (n = 18) were obtained from unculled litters. On postnatal day 150, Control, and Obese animals randomly received E. coli lipopolysaccharide (ALI) or saline (SAL) intratracheally. After 24 h, echocardiography, lung function and morphometry, and biological markers in lung tissue were evaluated. Additionally, mediator expression in neutrophils and macrophages obtained from blood and bronchoalveolar lavage fluid (BALF) was analyzed. Compared to Control-SAL animals, Control-ALI rats showed no changes in echocardiographic parameters, increased lung elastance and resistance, higher monocyte phagocytic capacity, collagen fiber content, myeloperoxidase (MPO) activity, and levels of interleukin (IL-6), tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, and type III (PCIII), and I (PCI) procollagen in lung tissue, as well as increased expressions of TNF-α and monocyte chemoattractant protein (MCP)-1 in blood and BALF neutrophils. Monocyte (blood) and macrophage (adipose tissue) phagocytic capacities were lower in Obese-ALI compared to Control-ALI animals, and Obese animals exhibited reduced neutrophil migration compared to Control. Obese-ALI animals, compared to Obese-SAL, exhibited increased interventricular septum thickness (p = 0.003) and posterior wall thickness (p = 0.003) and decreased pulmonary acceleration time to pulmonary ejection time ratio (p = 0.005); no changes in lung mechanics, IL-6, TNF-α, TGF-β, PCIII, and PCI in lung tissue; increased IL-10 levels in lung homogenate (p = 0.007); reduced MCP-1 expression in blood neutrophils (p = 0.009); decreased TNF-α expression in blood (p = 0.02) and BALF (p = 0.008) neutrophils; and increased IL-10 expression in monocytes (p = 0.004). In conclusion, after endotoxin challenge, obese rats showed less deterioration of lung function, secondary to anti-inflammatory and anti-fibrotic effects, as well as changes in neutrophil and monocyte/macrophage phenotype in blood and BALF compared to Control rats.

Highlights

20% of patients admitted to intensive care units (ICUs) are obese [1]
In Obese-SAL compared to Control-SAL animals, the internal diameter of the left ventricle was smaller, while interventricular septum thickness, posterior left ventricle wall thickness, and isovolumic relaxation time were greater; pulmonary acceleration time (PAT)/pulmonary ejection time (PET) ratio did not differ (Supplemental Figure S2)
Obesity led to decreased neutrophil migration

Summary

Introduction

20% of patients admitted to intensive care units (ICUs) are obese [1]. Observational studies have shown an association between obesity and increased risk for acute respiratory distress syndrome (ARDS) [2]. ARDSrelated mortality is lower in obese compared to non-obese patients [2,3,4,5]. All-cause ICU mortality is reduced in obese patients compared to ill non-obese ones, a phenomenon that has been termed the “obesity paradox” or “reverse epidemiology” [5,6,7]. In animals with acute lung injury (ALI), obesity has been shown to reduce the number of circulating monocytes and adhesion receptors, whereas alveolar macrophages develop a predominantly antiinflammatory phenotype [12]

Methods

Results

Conclusion