title: Dual role of IL-12 in the therapeutic efficacy or failure during combined PEG-Interferon-α2A and ribavirin therapy in patients with chronic hepatitis C.
abstract: Several efforts have been made to establish novel biomarkers with relevant predictive values to monitor HCV-infected patients under pegilated Interferon-α2A-(PEG-IFN-α2A)/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-α2A/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-α/IL-12/IFN-γ/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-α2A/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 CD8(+) 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-α2A/ribavirin therapy are closely related with the therapeutic response.
authors: Fundação de Medicina Tropical do Amazonas, Manaus, AM, Brazil; Universidade do Estado do Amazonas - UEA, Manaus, AM, Brazil; Universidade Federal do Amazonas, Manaus, AM, Brazil.
authors: Ana Ruth
authors: AR
authors: Araújo
authors: Vanessa
authors: V
authors: Peruhype-Magalhães
authors: Jordana Grazziela Alves
authors: JG
authors: Coelho-dos-Reis
authors: Laura Patrícia Viana
authors: LP
authors: Chaves
authors: Tatiane Amábili
authors: TA
authors: de Lima
authors: João Paulo Diniz
authors: JP
authors: Pimentel
authors: Lúcia
authors: L
authors: de Paula
authors: Carlos Maurício
authors: CM
authors: de Almeida
authors: Andréa Monteiro
authors: AM
authors: Tarragô
authors: Adriana
authors: A
authors: Tateno
authors: José Eduardo
authors: JE
authors: Levi
authors: Andrea
authors: A
authors: Teixeira-Carvalho
authors: Olindo de Assis
authors: OA
authors: Martins-Filho
authors: Edson da Fonseca
authors: Eda F
authors: Lira
authors: Kátia Luz
authors: KL
authors: Torres
authors: Sinésio
authors: S
authors: Talhari
authors: Adriana
authors: A
authors: Malheiro
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage; D054316:Biomarkers, Pharmacological / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000097:blood; D004359:Drug Therapy, Combination; D016174:Hepacivirus / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000008:administration & dosage; D018664:Interleukin-12 / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000008:administration & dosage; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D017211:Treatment Failure; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D054316:Biomarkers, Pharmacological; D016207:Cytokines; D016898:Interferon-alpha; D011994:Recombinant Proteins; D018664:Interleukin-12; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a
keywords: Cytokines; HCV; HCV non-responder; HCV-NR; PEG-IFN-α2A; PEG-IFN-α2A/ribavirin; SVR; Sustained virological response; Viral load; pegilated Interferon-α2A; sustained virological load