We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Correction of all-trans retinoic acid deficiency in alcoholic cirrhosis lessens the excessive inflammatory monocyte response: a translational study.
- Authors
Ouziel, Romy; Trépo, Eric; Cremer, Anneline; Moreno, Christophe; Degré, Delphine; Chaouni, Mustapha; Vercruysse, Vincent; Quertinmont, Eric; Devière, Jacques; Lemmers, Arnaud; Gustot, Thierry
- 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. 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. 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. 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.
- Subjects
LIVER diseases; VITAMIN A; IMMUNE response; TUMOR necrosis factors; PHYSIOLOGICAL effects of lipopolysaccharides
- Publication
Liver International, 2014, Vol 34, Issue 3, p343
- ISSN
1478-3223
- Publication type
Article
- DOI
10.1111/liv.12249