Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C
Modulation of the IL-12/IFN-γ axis by IFN-α therapy for hepatitis C
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DOI：
10.1189/jlb.1006622
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发表时间：
2007-03-01
影响因子：
5.5
通讯作者：
Karp, Christopher L.
中科院分区：
文献类型：
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作者：
Byrnes, Adriana A.;Li, Ding-You;Karp, Christopher L.
虽然ifn - α是慢性丙型肝炎治疗的基础，但只有少数患者仅对ifn - α有持续的反应。ifn - α的抗病毒活性是其用于病毒性肝炎的基本原理。然而，ifn - α和其他I型ifn也是多效性免疫调节因子。I型ifn可以通过激活STAT4促进ifn - γ的产生，但也可以抑制IL-12的产生，IL-12是STAT4和ifn - γ产生的有效激活剂。因此，ifn - α治疗丙型肝炎的疗效可能部分取决于ifn - γ诱导和il -12抑制作用的平衡。我们描述了聚乙二醇化ifn - α治疗丙型肝炎对患者PBMC体外产生IL-12和ifn - γ的能力的影响。来自对治疗有持续病毒学反应的患者的C细胞在治疗前显著高于来自无反应患者的ifn - α驱动的ifn - γ产生水平。患者组间预处理IL-12生产能力无差异。然而，在两组患者的整个治疗过程中，ifn - α治疗导致诱导性IL-12的产生受到抑制。
Although IFN-alpha forms the foundation of therapy for chronic hepatitis C, only a minority of patients has a sustained response to IFN-alpha alone. The antiviral activities of IFN-alpha formed the rationale for its use in viral hepatitis. However, IFN-alpha and the other Type I IFNs are also pleiotropic immune regulators. Type I IFNs can promote IFN-gamma production by activating STAT4 but can also inhibit production of IL-12, a potent activator of STAT4 and IFN-gamma production. The efficacy of IFN-alpha in the treatment of hepatitis C may therefore depend in part on the balance of IFN-gamma-inducing and IL-12-suppressing effects. We characterized the effects of pegylated IFN-alpha therapy for hepatitis C on the capacity of patients' PBMC to produce IL-12 and IFN-gamma ex vivo. C ells from patients with a sustained virological response to therapy had significantly greater levels of IFN-alpha-driven IFN-gamma production prior to treatment than those from nonresponding patients. No differences in pretreatment IL-12 productive capacity were seen between patient groups. However, therapy with IFN-alpha led to suppression of inducible IL-12 production throughout the course of therapy in both groups of patients.