Article
CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice
Registro en:
FERRERO, Maximiliano Ruben et al. CCR5 Antagonist Maraviroc Inhibits Acute Exacerbation of Lung Inflammation Triggered by Influenza Virus in Cigarette Smoke-Exposed Mice. Pharmaceuticals, v. 14, n. 620, 14 p, June 2021.
1999-4923
10.3390/ph14070620
Autor
Ferrero, Maximiliano Ruben
Garcia, Cristiana Couto
Almeida, Marcella Dutra de
Silva, Jullian Torres Braz da
Insuela, Daniella Bianchi Reis
Ferreira, Tatiana Paula Teixeira
Coutinho, Diego de Sá
Azevedo, Carolina Trindade de
Silva, Patrícia Machado Rodrigues e
Martins, Marco Aurélio
Resumen
Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic
obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 α, a chemokine
that acts through CC-chemokine receptor (CCR)-5, appears elevated in COPD patients’ airways,
we evaluated whether CCR5 antagonist Maraviroc could inhibit the exacerbated lung inflamma tory response noted after IAV H1N1 infection in mice exposed to cigarette smoke (Cs). C57BL/6
mice, subjected or not to Cs inhalation for 11 days, were infected with H1N1 at day 7. Maraviroc
(10 mg/kg) or dexamethasone (1 mg/kg) were given in a therapeutic schedule, followed by the
analyses of lung function, survival rate, and inflammatory changes. As compared to mice subjected
to Cs or H1N1 alone, the insult combination significantly worsened airway obstruction, neutrophil
infiltration in the airways, and the survival rate. All changes were sensitive to Maraviroc but not
dexamethasone. Maraviroc also reduced the accumulation of neutrophils and macrophages as well
as CXCL1 production in the lung tissue, and serum levels of IL-6, whereas comparable viral titers in
the lungs were noted in all infected groups. Collectively, these findings suggest that Maraviroc oral
treatment could be an effective therapy for controlling acute exacerbations of respiratory diseases
such as COPD.