Dual role of IL-12 in the therapeutic efficacy or failure during combined PEG-Interferon-¦Á2A and ribavirin therapy in patients with chronic hepatitis C

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• 作者：Ana Ruth Ara¨²jo ; Vanessa Peruhype-Magalh?es ; Jordana Grazziela Alves Coelho-dos-Reis ; Laura Patr¨ªcia Viana Chaves ; Tatiane Am¨¢bili de Lima ; Jo?o Paulo Diniz Pimentel ; L¨²cia de Paula ; Carlos Maur¨ªcio de Almeida ; Andr¨¦a Monteiro Tarrag? ; Adriana Tateno ; Jos¨¦ Eduardo Levi ; Andrea Teixeira-Carvalho ; Olindo de Assis Martins-Filho ; Edson da Fonseca Lira ; K¨¢tia Luz Torres ; Sin¨¦sio Talhari ; Adriana Malheiro
• 关键词：SVR ; sustained virological load ; HCV-NR ; HCV non-responder ; PEG-IFN-¦Á2A ; pegilated Interferon-¦Á2A
• 刊名：Immunology Letters
• 出版年：2013
• 出版时间：July-August, 2013
• 年：2013
• 卷：154
• 期：1-2
• 页码：61-69
• 全文大小：1220 K

文摘

Several efforts have been made to establish novel biomarkers with relevant predictive values to monitor HCV-infected patients under pegilated Interferon-¦Á2A-(PEG-IFN-¦Á2A)/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-¦Á2A/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-¦Á/IL-12/IFN-¦Ã/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-¦Á2A/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-¦Á2A/ribavirin therapy are closely related with the therapeutic response.