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Colchicine reduces lung injury in experimental acute respiratory distress syndrome.
Dupuis, Jocelyn; Sirois, Martin G; Rhéaume, Eric; Nguyen, Quang T; Clavet-Lanthier, Marie-Élaine; Brand, Genevieve; Mihalache-Avram, Teodora; Théberge-Julien, Gabriel; Charpentier, Daniel; Rhainds, David; Neagoe, Paul-Eduard; Tardif, Jean-Claude.
  • Dupuis J; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Sirois MG; Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
  • Rhéaume E; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Nguyen QT; Department of Pharmacology and Physiology, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
  • Clavet-Lanthier MÉ; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Brand G; Department of Medicine, Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
  • Mihalache-Avram T; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Théberge-Julien G; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Charpentier D; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Rhainds D; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Neagoe PE; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
  • Tardif JC; Montreal Heart Institute Research Center, Montreal, Quebec, Canada.
PLoS One ; 15(12): e0242318, 2020.
Article in English | MEDLINE | ID: covidwho-955356
ABSTRACT
The acute respiratory distress syndrome (ARDS) is characterized by intense dysregulated inflammation leading to acute lung injury (ALI) and respiratory failure. There are no effective pharmacologic therapies for ARDS. Colchicine is a low-cost, widely available drug, effective in the treatment of inflammatory conditions. We studied the effects of colchicine pre-treatment on oleic acid-induced ARDS in rats. Rats were treated with colchicine (1 mg/kg) or placebo for three days prior to intravenous oleic acid-induced ALI (150 mg/kg). Four hours later they were studied and compared to a sham group. Colchicine reduced the area of histological lung injury by 61%, reduced lung edema, and markedly improved oxygenation by increasing PaO2/FiO2 from 66 ± 13 mmHg (mean ± SEM) to 246 ± 45 mmHg compared to 380 ± 18 mmHg in sham animals. Colchicine also reduced PaCO2 and respiratory acidosis. Lung neutrophil recruitment, assessed by myeloperoxidase immunostaining, was greatly increased after injury from 1.16 ± 0.19% to 8.86 ± 0.66% and significantly reduced by colchicine to 5.95 ± 1.13%. Increased lung NETosis was also reduced by therapy. Circulating leukocytosis after ALI was not reduced by colchicine therapy, but neutrophils reactivity and CD4 and CD8 cell surface expression on lymphocyte populations were restored. Colchicine reduces ALI and respiratory failure in experimental ARDS in relation with reduced lung neutrophil recruitment and reduced circulating leukocyte activation. This study supports the clinical development of colchicine for the prevention of ARDS in conditions causing ALI.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Colchicine / Acute Lung Injury / Lung Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2020 Document Type: Article Affiliation country: Journal.pone.0242318

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Respiratory Distress Syndrome / Colchicine / Acute Lung Injury / Lung Type of study: Prognostic study / Randomized controlled trials Limits: Animals / Humans Language: English Journal: PLoS One Journal subject: Science / Medicine Year: 2020 Document Type: Article Affiliation country: Journal.pone.0242318