Ghrelin therapy improves lung and cardiovascular function in experimental emphysema

• Published in: Respiratory research Vol. 18; no. 1; p. 185
• Main Authors: Rocha, Nazareth de Novaes, de Oliveira, Milena Vasconcellos, Braga, Cássia Lisboa, Guimarães, Gabriela, Maia, Lígia de Albuquerque, Padilha, Gisele de Araújo, Silva, Johnatas Dutra, Takiya, Christina Maeda, Capelozzi, Vera Luiza, Silva, Pedro Leme, Rocco, Patricia Rieken Macedo
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 03.11.2017; BioMed Central; BMC
• Subjects: Airspace; Alveoli; Animals; Biological effects; Body composition; Body mass; Body size; Cardiac function; Cardiovascular system; Care and treatment; Chronic obstructive pulmonary disease; Collagen; Complications and side effects; Cytokines; Dosage and administration; Dual energy X-ray absorptiometry; Echocardiography; Elastase; Emphysema; Enlargement; Experimental emphysema; Extracellular matrix; Ghrelin; Ghrelin therapy; Growth factors; Histology; Hypertension; Hypertrophy; Infiltration; Inflammation; Interleukin 10; Interleukin 8; Interleukins; Laboratory animals; Lung function; Lung inflammation; Lung remodelling; Lungs; Macrophages; Mechanics; Mechanics (physics); Medical prognosis; Metastases; Molecular biology; Muscles; Pancreas; Patient outcomes; Pulmonary arteries; Respiratory function; Rodents; Septum; Therapy; Trachea; Transforming growth factor-b; Tumor necrosis factor; Tumors; Vasodilation; Ventricle; Brazil; Lung inflammation; Lung function; Lung remodelling; Ghrelin therapy; Cardiac function; Experimental emphysema
• ISSN: 1465-993X; 1465-9921; 1465-993X; 1465-9921
• DOI: 10.1186/s12931-017-0668-9

Emphysema is a progressive disease characterized by irreversible airspace enlargement followed by a decline in lung function. It also causes extrapulmonary effects, such as loss of body mass and cor pulmonale, which are associated with shorter survival and worse clinical outcomes. Ghrelin, a growth-hormone secretagogue, stimulates muscle anabolism, has anti-inflammatory effects, promotes vasodilation, and improves cardiac performance. Therefore, we hypothesized that ghrelin might reduce lung inflammation and remodelling as well as improve lung mechanics and cardiac function in experimental emphysema. Forty female C57BL/6 mice were randomly assigned into two main groups: control (C) and emphysema (ELA). In the ELA group (n=20), animals received four intratracheal instillations of pancreatic porcine elastase (PPE) at 1-week intervals. C animals (n=20) received saline alone (50 μL) using the same protocol. Two weeks after the last instillation of saline or PPE, C and ELA animals received ghrelin or saline (n=10/group) intraperitoneally (i.p.) daily, during 3 weeks. Dual-energy X-ray absorptiometry (DEXA), echocardiography, lung mechanics, histology, and molecular biology were analysed. In elastase-induced emphysema, ghrelin treatment decreased alveolar hyperinflation and mean linear intercept, neutrophil infiltration, and collagen fibre content in the alveolar septa and pulmonary vessel wall; increased elastic fibre content; reduced M1-macrophage populations and increased M2 polarization; decreased levels of keratinocyte-derived chemokine (KC, a mouse analogue of interleukin-8), tumour necrosis factor-α, and transforming growth factor-β, but increased interleukin-10 in lung tissue; augmented static lung elastance; reduced arterial pulmonary hypertension and right ventricular hypertrophy on echocardiography; and increased lean mass. In the elastase-induced emphysema model used herein, ghrelin not only reduced lung damage but also improved cardiac function and increased lean mass. These findings should prompt further studies to evaluate ghrelin as a potential therapy for emphysema.