Mesenteric Th1 polarization and monocyte TNF-α production: First steps to systemic inflammation in rats with cirrhosis
Authors
Muñoz, Leticia; Albillos Martínez, Agustín; Nieto González, Mónica; Lledó García, María Lourdes; Monserrat Sanz, Jorge; [et al.]Identifiers
Permanent link (URI): http://hdl.handle.net/10017/61255DOI: 10.1002/hep.20799
ISSN: 0270-9139
Date
2005-07-15Bibliographic citation
Hepatology, 2005, v. 42, n. 2, p. 411-419
Document type
info:eu-repo/semantics/article
Version
info:eu-repo/semantics/aceptedVersion
Rights
Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
© 2005 by the American Association for the Study of Liver Diseases
Access rights
info:eu-repo/semantics/openAccess
Abstract
A systemic inflammatory state with increased circulating tumor necrosis factor alpha (TNF-alpha) has been related to the bacterial infection susceptibility and hemodynamic derangement of patients with. cirrhosis. We compared the activation status of immune cell subpopulations defined by 4-color cytometry in mesenteric and peripheral lymph nodes and blood of rats with CCl4-cirrhosis to define the immune response initiation site, the T-cell and monocyte contribution to pro-inflammatory cytokine production, as well as the pathogenic role of enteric bacteria in the cirrhosis immune response. Th1 cells and monocytes were expanded in the mesenteric nodes (P < .001) and blood (P < .001) of rats with cirrhosis, and activated to produce interferon gamma (P < .0001) and TNF-a (P < .0001), respectively. The greater numbers of recently activated CD134(+) Th cells in mesenteric nodes compared with blood, the correlation between their numbers in mesenteric nodes and blood (r = 0.66, P < .001), and the expansion of activated CD45RC(-) Th cells, which are unable to re-enter lymph nodes, in mesenteric nodes but not in blood or axillary nodes points to mesenteric nodes as the origin site of activated Th cells. Abrogation of bacterial translocation by bowel decontamination reduced the number of activated Th cells and monocytes, and normalized interferon gamma production by Th cells and TNF-alpha production by monocytes in mesenteric nodes and blood, respectively. In conclusion, in cirrhosis, enteric bacteria start off an orchestrated immune response cascade in mesenteric nodes involving Th1 polarization and monocyte activation to TNF-alpha production. Later, the recirculation of these activated effector immune cells into blood promotes systemic inflammation.
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