Colchicine reduces lung injury in experimental acute respiratory distress syndrome

PLoS One. 2020 Dec 2;15(12):e0242318. doi: 10.1371/journal.pone.0242318. eCollection 2020.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / blood
  • Acute Lung Injury / chemically induced
  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / pathology
  • Animals
  • Colchicine / pharmacology*
  • Disease Models, Animal
  • Humans
  • Lung / drug effects*
  • Lung / pathology
  • Neutrophil Infiltration / drug effects
  • Neutrophils / drug effects
  • Oleic Acid / toxicity
  • Rats
  • Respiratory Distress Syndrome / blood
  • Respiratory Distress Syndrome / chemically induced
  • Respiratory Distress Syndrome / drug therapy*
  • Respiratory Distress Syndrome / pathology

Substances

  • Oleic Acid
  • Colchicine

Grant support

This study was funded by the Government of Quebec and the Canada Research Chair in translational and personalized medicine held by J-CT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.