In:
PLOS ONE, Public Library of Science (PLoS), Vol. 15, No. 12 ( 2020-12-2), p. e0242318-
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 PaO 2 /FiO 2 from 66 ± 13 mmHg (mean ± SEM) to 246 ± 45 mmHg compared to 380 ± 18 mmHg in sham animals. Colchicine also reduced PaCO 2 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.
Type of Medium:
Online Resource
ISSN:
1932-6203
DOI:
10.1371/journal.pone.0242318
DOI:
10.1371/journal.pone.0242318.g001
DOI:
10.1371/journal.pone.0242318.g002
DOI:
10.1371/journal.pone.0242318.g003
DOI:
10.1371/journal.pone.0242318.g004
DOI:
10.1371/journal.pone.0242318.g005
DOI:
10.1371/journal.pone.0242318.t001
DOI:
10.1371/journal.pone.0242318.s001
DOI:
10.1371/journal.pone.0242318.s002
DOI:
10.1371/journal.pone.0242318.r001
DOI:
10.1371/journal.pone.0242318.r002
DOI:
10.1371/journal.pone.0242318.r003
DOI:
10.1371/journal.pone.0242318.r004
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2020
detail.hit.zdb_id:
2267670-3
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