Inosine exerts a broad range of antiinflammatory effects in a murine model of acute lung injury

Détails

ID Serval
serval:BIB_7B5D2D6DC209
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Inosine exerts a broad range of antiinflammatory effects in a murine model of acute lung injury
Périodique
Annals of Surgery
Auteur(s)
Liaudet  L., Mabley  J. G., Pacher  P., Virag  L., Soriano  F. G., Marton  A., Hasko  G., Deitch  E. A., Szabo  C.
ISSN
0003-4932 (Print)
Statut éditorial
Publié
Date de publication
04/2002
Volume
235
Numéro
4
Pages
568-78
Notes
In Vitro
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Apr
Résumé
OBJECTIVE: To investigate the effects of inosine on the acute lung inflammation induced by lipopolysaccharide (LPS) in vivo and on the activation and cytotoxicity elicited by proinflammatory cytokines on human lung epithelial (A549) cells in vitro. SUMMARY BACKGROUND DATA: Inosine is an endogenous purine recently shown to exert immunomodulatory and antiinflammatory effects. METHODS: Mice challenged with intratracheal LPS (50 microg) were treated after 1, 6, and 12 hours with inosine (200 mg/kg intraperitoneal) or vehicle. After 24 hours, bronchoalveolar lavage fluid was obtained to measure proinflammatory (tumor necrosis factor-alpha [TNF-alpha], interleukin [IL]-1beta, IL-6), and antiinflammatory (IL-10, IL-4) cytokines, chemokines (MIP-1alpha and MIP-2), myeloperoxidase activity and total cell counts, nitric oxide production, and proteins. Lung histology and immunohistochemical detection of 3-nitrotyrosine, a marker of nitrosative stress, were performed in inflated-fixed lungs. In vitro, cell viability and production of the chemokine IL-8 were evaluated in A549 cells stimulated with a mixture of cytokines in the presence or absence of inosine. RESULTS: Inosine downregulated the LPS-induced expression of TNF-alpha, IL-1beta, IL-6 and MIP-2 and tended to reduce MIP-1alpha, whereas it enhanced the production of IL-4. Total leukocyte counts, myeloperoxidase, nitric oxide production, and proteins were all significantly decreased by inosine. The purine also improved lung morphology and suppressed 3-nitrotyrosine staining in the lungs after LPS. Inosine attenuated the cytotoxicity and the expression of IL-8 induced by proinflammatory cytokines in A549 cells. CONCLUSIONS: Inosine largely suppressed LPS-induced lung inflammation in vivo and reduced the toxicity of cytokines in lung cells in vitro. These data support the proposal that inosine might represent a useful adjunct in the therapy of acute respiratory distress syndrome.
Mots-clé
Animals Anti-Inflammatory Agents/*therapeutic use Cell Line Cytokines/*drug effects Disease Models, Animal Epithelial Cells/*drug effects Escherichia coli/*pathogenicity Humans Inosine/*therapeutic use Lipopolysaccharides/*adverse effects Lung/*drug effects Male Mice Mice, Inbred BALB C Respiratory Distress Syndrome, Adult/*chemically induced/*drug therapy
Pubmed
Web of science
Création de la notice
24/01/2008 18:01
Dernière modification de la notice
03/03/2018 18:35
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