Low-Dose Colchicine Attenuates Sepsis-Induced Liver Injury: A Novel Method for Alleviating Systemic Inflammation.
Colchicine
Gut immune system
Immunomodulation
Microtubules
Sepsis
Journal
Inflammation
ISSN: 1573-2576
Titre abrégé: Inflammation
Pays: United States
ID NLM: 7600105
Informations de publication
Date de publication:
Jun 2023
Jun 2023
Historique:
received:
09
08
2022
accepted:
09
01
2023
revised:
06
01
2023
medline:
18
5
2023
pubmed:
20
1
2023
entrez:
19
1
2023
Statut:
ppublish
Résumé
Sepsis is a significant public health challenge. The immune system underlies the pathogenesis of the disease. The liver is both an active player and a target organ in sepsis. Targeting the gut immune system using low-dose colchicine is an attractive method for alleviating systemic inflammation in sepsis without inducing immunosuppression. The present study aimed to determine the use of low-dose colchicine in LPS-induced sepsis in mice. C67B mice were injected intraperitoneal with LPS to induce sepsis. The treatment group received 0.02 mg/kg colchicine daily by gavage. Short and extended models were performed, lasting 3 and 5 days, respectively. We followed the mice for biochemical markers of end-organ injury, blood counts, cytokine levels, and liver pathology and conducted proteomic studies on liver samples. Targeting the gut immune system using low-dose colchicine improved mice's well-being measured by the murine sepsis score. Treatment alleviated the liver injury in septic mice, manifested by a significant decrease in their liver enzyme levels, including ALT, AST, and LDH. Treatment exerted a trend to reduce creatinine levels. Low-dose colchicine improved liver pathology, reduced inflammation, and reduced the pro-inflammatory cytokine TNFα and IL1-β levels. A liver proteomic analysis revealed low-dose colchicine down-regulated sepsis-related proteins, alpha-1 antitrypsin, and serine dehydratase. Targeting the gut immune system using low-dose colchicine attenuated liver injury in LPS-induced sepsis, reducing the pro-inflammatory cytokine levels. Low-dose colchicine provides a safe method for immunomodulation for multiple inflammatory disorders.
Identifiants
pubmed: 36656466
doi: 10.1007/s10753-023-01783-9
pii: 10.1007/s10753-023-01783-9
doi:
Substances chimiques
Colchicine
SML2Y3J35T
Lipopolysaccharides
0
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
963-974Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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