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Changes in cellular proliferation and plasma products are associated with liver failure

World Journal of Hepatology 2016年第32期8卷 1370-1383页

作者： Juliana Gil Melgaco Frederico Marianetti Soriani Pedro Henrique Ferreira Sucupira Leonardo Assaf Pinheiro Yasmine Rangel Vieira Jaqueline Mendes de Oliveira Lia Laura Lewis-Ximenez Cristina Carvalho Vianna Araújo Lúcio Filgueiras Pacheco-Moreira Gustavo Batista Menezes Oswaldo Goncalves Cruz claudia lamarca vitral Marcelo Alves Pinto Departamento de Microbiologia e Parasitologia Universidade Federal Fluminense Instituto Oswaldo Cruz/Fiocruz Laboratório de Desenvolvimento Tecnológico em Virologia Departamento de Biologia Geral Instituto de Ciencias BiologicasUniversidade Federal de Minas Gerais Instituto Oswaldo Cruz/Fiocruz Ambulatório de Hepatites Virais Hospital Federal de Bonsucesso Laboratório de Imunofarmacologia Departamento de Bioquímica e ImunologiaInstituto de Ciencias BiológicasUniversidade Federal de Minas Gerais Fundacao Oswaldo Cruz Programa de Computacao Científica

AIM To study the differences in immune response and cytokine profile between acute liver failure and selflimited acute *** Forty-six patients with self-limited acute hepatitis(AH), sixteen patients with acute liver failure(ALF), and twenty-two healthy subjects were involved in this study. The inflammatory and anti-inflammatory products in plasma samples were quantified using commercial enzyme-linked immunoassays and quantitative real-time PCR. The cellular immune responses were measured by proliferation assay using flow cytometry. The groups were divided into viral- and non-viral-induced selflimited AH and ALF. Thus, we worked with five groups: Hepatitis A virus(HAV)-induced self-limited acute hepatitis(HAV-AH), HAV-induced ALF(HAV-ALF), nonviral-induced self-limited acute hepatitis(non-viral AH), non-viral-induced acute liver failure(non-viral ALF), and healthy subjects(HC). Comparisons among HAV and non-viral-induced AH and ALF were *** The levels of mitochondrial DNA(mt DNA) and the cytokines investigated [interleukin(IL)-6, IL-8, IL-10, interferon gamma, and tumor necrosis factor] were significantly increased in ALF patients, independently of etiology(P < 0.05). High plasma mt DNA and IL-10 were the best markers associated with ALF [mt DNA: OR = 320.5(95%CI: 14.42-7123.33), P < 0.0001; and IL-10: OR = 18.8(95%CI: 1.38-257.94), P = 0.028] and death [mt DNA: OR = 12.1(95%CI: 2.57-57.07), P = 0.002; and IL-10: OR = 8.01(95%CI: 1.26-50.97), P = 0.027]. In the cellular proliferation assay, NK^(bright), NKT and regulatory T cells(TReg) predominated in virusspecific stimulation in HAV-induced ALF patients with an anergic behavior in the cellular response to mitotic stimulation. Therefore, in non-viral-induced ALF, anergic behavior of activated T cells was not observed after mitotic stimulation, as expected and as described by the literature. CONCLUSION mt DNA and IL-10 may be predictors of ALF and death. TReg cells are involved in immunologi

关键词： Acute liver failure Cytokines Mitochondrial DNA Cellular immune response Hepatitis A virus

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