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Front. Immunol. | doi: 10.3389/fimmu.2019.01215

Effects of obesity on pulmonary inflammation and remodeling in experimental moderate acute lung injury

 Lígia D. Maia1,  Fernanda F. Cruz1,  Milena V. De Oliveira1,  Cynthia S. Samary1,  Marcos V. Fernandes1, Stefano D. Trivelin1, Nazareth d. Rocha2, Marcelo Gama de Abreu3, Paolo Pelosi4,  Pedro L. Silva1 and  Patricia R. Rocco1*
  • 1Federal University of Rio de Janeiro, Brazil
  • 2Universidade Federal Fluminense, Brazil
  • 3Dresden University of Technology, Germany
  • 4University of Genoa, Italy

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 24h, 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 and. 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 antifibrotic effects, as well as changes in neutrophil and monocyte/macrophage phenotype in blood and BALF compared to Control rats.

Keywords: Obesity, Neutrophil, macrophage, remodeling, Acute Respiratory Distress Syndrome, Lung Histology

Received: 12 Dec 2018; Accepted: 13 May 2019.

Edited by:

Rudolf Lucas, Medical College of Georgia, Augusta University, United States

Reviewed by:

Juerg Hamacher, Lindenhofspital, Switzerland
Benjamin Suratt, University of Vermont, United States  

Copyright: © 2019 Maia, Cruz, De Oliveira, Samary, Fernandes, Trivelin, Rocha, Gama de Abreu, Pelosi, Silva and Rocco. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Patricia R. Rocco, Federal University of Rio de Janeiro, Rio de Janeiro, 21941-901, Rio de Janeiro, Brazil,