期刊
PHARMACEUTICALS
卷 14, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/ph14070620
关键词
chemokine receptor; chronic obstructive pulmonary disease; Maraviroc
资金
- Fundacao Carlos Chagas de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ)
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil
The study found that in cigarette smoke-exposed mice, H1N1 infection exacerbated airway obstruction, neutrophil infiltration, and reduced survival rate. However, the CCR5 antagonist Maraviroc significantly attenuated these inflammatory responses, suggesting it could be an effective therapy for controlling acute exacerbations of respiratory diseases such as COPD.
Influenza A virus (IAV) infection is a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). Since macrophage inflammatory protein 1 alpha, 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 inflammatory 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.
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