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Correction of all-trans retinoic acid deficiency in alcoholic cirrhosis lessens the excessive inflammatory monocyte response: a translational study.
- Source :
-
Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2014 Mar; Vol. 34 (3), pp. 343-52. Date of Electronic Publication: 2013 Jul 08. - Publication Year :
- 2014
-
Abstract
- Background & Aims: Patients with alcoholic liver disease (ALD) have vitamin A (VA) deficiency and an enhanced immune response associated with disease severity. All-trans retinoic acid (ATRA), a VA-active metabolite, has anti-inflammatory effects and its deficiency could contribute to the exacerbated proinflammatory reaction. The aim of this study was to investigate the effects of ATRA/VA deficiency and supplementation on the monocyte response in ALD.<br />Methods: Vitamin A and ATRA plasma levels were quantified in ALD patients and healthy subjects (HS). The in vitro effect of ATRA on lipopolysaccharide (LPS)-induced TNF-α production by human peripheral blood mononuclear cells (PBMC) was assessed by ELISA and RT-PCR. The activation pattern of peritoneal macrophages (PerMΦ) and circulating monocytes isolated from VA-deficient mice and ALD patients, respectively, was evaluated by flow cytometry, quantification of TNF-α and NO2 production.<br />Results: Alcoholic liver disease patients (n = 85) showed plasmatic VA deficiency that was correlated with scores of severity and with the hepatic venous pressure gradient. ATRA levels correlated significantly with VA levels. In vitro, ATRA pretreatment decreased the overproduction of TNF-α by LPS-stimulated PBMC of ALD patients. In vivo, VA deficiency in mice was associated with increased activation of PerMΦ, while oral ATRA supplementation normalized it.<br />Conclusion: For the first time, we show that VA/ATRA deficiencies in ALD patients are associated with disease severity. Furthermore, our data strongly suggest that the VA deficiency observed in ALD patients might participate in the pathophysiology of the disease by priming immune cells, and that ATRA supplementation could downregulate the deleterious proinflammatory state in cirrhosis and might thus be of therapeutic use.<br /> (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
- Subjects :
- Adult
Aged
Animals
Case-Control Studies
Cells, Cultured
Disease Models, Animal
Down-Regulation
Female
Humans
Lipopolysaccharides pharmacology
Macrophage Activation immunology
Macrophages, Peritoneal immunology
Male
Mice
Mice, Inbred C57BL
Middle Aged
RNA, Messenger genetics
Vitamin A blood
Liver Cirrhosis, Alcoholic immunology
Monocytes immunology
Tretinoin blood
Tretinoin pharmacology
Tumor Necrosis Factor-alpha metabolism
Vitamin A Deficiency complications
Subjects
Details
- Language :
- English
- ISSN :
- 1478-3231
- Volume :
- 34
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Liver international : official journal of the International Association for the Study of the Liver
- Publication Type :
- Academic Journal
- Accession number :
- 23834309
- Full Text :
- https://doi.org/10.1111/liv.12249