Dual role of IL-12 in the therapeutic efficacy or failure during combined PEG-Interferon-alpha 2A and ribavirin therapy in patients with chronic hepatitis C

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dc.contributor Sistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.author ARAUJO, Ana Ruth
PERUHYPE-MAGALHAES, Vanessa
COELHO-DOS-REIS, Jordana Grazziela Alves
CHAVES, Laura Patricia Viana
LIMA, Tatiane Amabili de
PIMENTEL, Joao Paulo Diniz
PAULA, Lucia de
ALMEIDA, Carlos Mauricio de
TARRAGO, Andrea Monteiro
TATENO, Adriana FMUSP-HC
LEVI, Jose Eduardo FMUSP-HC
TEIXEIRA-CARVALHO, Andrea
MARTINS-FILHO, Olindo de Assis
LIRA, Edson da Fonseca
TORRES, Katia Luz
TALHARI, Sinesio
MALHEIRO, Adriana
dc.date.issued 2013
dc.identifier.citation IMMUNOLOGY LETTERS, v.154, n.1-2, p.61-69, 2013
dc.identifier.issn 0165-2478
dc.identifier.uri http://observatorio.fm.usp.br/handle/OPI/4498
dc.description.abstract Several efforts have been made to establish novel biomarkers with relevant predictive values to monitor HCV-infected patients under pegilated Interferon-alpha 2A-(PEG-IFN-alpha 2A)/ribavirin therapy. The aim of this study was to monitor the kinetics of HCV viral load, serum levels of pro-inflammatory/regulatory cytokines and leukocyte activation status before and after PEG-IFN-alpha 2A/ribavirin therapy in 52 volunteers, including 12 chronic HCV patients and 40 controls. The HCV viral load, serum levels of cytokines (IL-8/IL-6/TNF-alpha/IL-12/IFN-gamma/IL-4/IL-10) and the phenotype of peripheral blood leukocytes were evaluated before and after 4, 12 and 24 weeks following the PEG-IFN-alpha 2A/ribavirin therapy. Our results demonstrated that sustained virological response-(SVR) is associated with early decrease in the viral load after 4 weeks of treatment. The presence of a modulated pro-inflammatory profile at baseline favors SVR, whereas a strong inflammatory response at baseline predisposes to therapeutic failure. Furthermore, a time-dependent increase on serum IL-12 levels in patients under treatment is critical to support the SVR, while the early predominance of IL-10 correlates to late virological relapse. On the other hand, a broad but unguided ""cytokine storm"" is observed in the non-responder HCV patients after 12 weeks of treatment. Corroborating these findings, monocyte/lymphocyte activation at baseline is associated with the non-responders to therapy whereas high CDS+ T-cell numbers associate with SVR. All in all, these data suggest that the baseline pattern of serum pro-inflammatory/regulatory cytokines and the immunological activation status of chronic HCV patients undergoing PEG-IFN-alpha 2A/ribavirin therapy are closely related with the therapeutic response.
dc.description.sponsorship · Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG), Brazil
· Fundacao de Amparo a Pesquisa do Estado do Amazonas (FAPEAM)
· Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
dc.language.iso eng
dc.publisher ELSEVIER SCIENCE BV
dc.relation.ispartof Immunology Letters
dc.rights restrictedAccess
dc.subject HCV; PEG-IFN-alpha 2A/ribavirin; Viral load; Cytokines
dc.subject.other sustained virological response; interferon-alpha therapy; virus-infection; pretreatment prediction; pegylated-interferon; plus ribavirin; host factors; t-cells; peginterferon; polymorphisms
dc.title Dual role of IL-12 in the therapeutic efficacy or failure during combined PEG-Interferon-alpha 2A and ribavirin therapy in patients with chronic hepatitis C
dc.type article
dc.rights.holder Copyright ELSEVIER SCIENCE BV
dc.description.group LIM/52
dc.identifier.doi 10.1016/j.imlet.2013.07.010
dc.identifier.pmid 23973662
dc.type.category original article
dc.type.version publishedVersion
hcfmusp.author TATENO, Adriana:IMT:
hcfmusp.author LEVI, Jose Eduardo:HC:INCOR
hcfmusp.author.external · ARAUJO, Ana Ruth:Fundacao Med Trop Amazonas, Manaus, Amazonas, Brazil; Univ Estado Amazonas, Manaus, Amazonas, Brazil; Univ Fed Amazonas, Manaus, Amazonas, Brazil
· PERUHYPE-MAGALHAES, Vanessa:Fundacao Oswaldo Cruz, Lab Biomarcadores Diagnost & Monitoracao, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil
· COELHO-DOS-REIS, Jordana Grazziela Alves:Fundacao Oswaldo Cruz, Lab Biomarcadores Diagnost & Monitoracao, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil
· CHAVES, Laura Patricia Viana:Univ Fed Amazonas, Manaus, Amazonas, Brazil; Fundacao Hematol & Hemoterapia Amazonas Hemoam, Manaus, Amazonas, Brazil
· LIMA, Tatiane Amabili de:Fundacao Med Trop Amazonas, Manaus, Amazonas, Brazil; Univ Estado Amazonas, Manaus, Amazonas, Brazil; Fundacao Hematol & Hemoterapia Amazonas Hemoam, Manaus, Amazonas, Brazil
· PIMENTEL, Joao Paulo Diniz:Fundacao Hematol & Hemoterapia Amazonas Hemoam, Manaus, Amazonas, Brazil; FIOCRUZ Amazonia, Ctr Pesquisas Leonidas & Maria Deane, Manaus, Amazonas, Brazil
· PAULA, Lucia de:Univ Fed Amazonas, Manaus, Amazonas, Brazil; Fundacao Alfredo da Matta FUAM, Manaus, Amazonas, Brazil
· ALMEIDA, Carlos Mauricio de:Fundacao Med Trop Amazonas, Manaus, Amazonas, Brazil
· TARRAGO, Andrea Monteiro:Univ Fed Amazonas, Manaus, Amazonas, Brazil; Fundacao Hematol & Hemoterapia Amazonas Hemoam, Manaus, Amazonas, Brazil
· TEIXEIRA-CARVALHO, Andrea:Fundacao Oswaldo Cruz, Lab Biomarcadores Diagnost & Monitoracao, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil
· MARTINS-FILHO, Olindo de Assis:Fundacao Oswaldo Cruz, Lab Biomarcadores Diagnost & Monitoracao, Ctr Pesquisas Rene Rachou, Belo Horizonte, MG, Brazil
· LIRA, Edson da Fonseca:Fundacao Hematol & Hemoterapia Amazonas Hemoam, Manaus, Amazonas, Brazil
· TORRES, Katia Luz:Fundacao Hematol & Hemoterapia Amazonas Hemoam, Manaus, Amazonas, Brazil
· TALHARI, Sinesio:Fundacao Med Trop Amazonas, Manaus, Amazonas, Brazil; Univ Estado Amazonas, Manaus, Amazonas, Brazil
· MALHEIRO, Adriana:Univ Fed Amazonas, Manaus, Amazonas, Brazil; Fundacao Hematol & Hemoterapia Amazonas Hemoam, Manaus, Amazonas, Brazil
hcfmusp.origem.id WOS:000326559400010
hcfmusp.origem.id 2-s2.0-84884200778
hcfmusp.publisher.city AMSTERDAM
hcfmusp.publisher.country NETHERLANDS
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dc.description.index MEDLINE
hcfmusp.citation.scopus 5
hcfmusp.citation.wos 4
hcfmusp.affiliation.country Brasil


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