Department of Internal Medicine I, University of Bonn, Bonn, Germany.
J Hepatol. 2011 May;54(5):859-65. doi: 10.1016/j.jhep.2010.08.020. Epub 2010 Oct 23.
BACKGROUND & AIMS: Dendritic cells (DCs) trigger adaptive immune responses and are an important source of antiviral cytokines. In hepatitis C virus (HCV) infection DC function is markedly impaired. Thus far, studies have focused on types I and II interferon (IFN). We studied IFN-lambda1 (IL-29) and IFN-lambda2/3 (IL-28A/B) serum levels in patients with different outcomes of HCV infection.
IFN-lambdas were measured by ELISAs detecting IL-29 or IL-28A and IL-28B, respectively. Results were stratified with respect to the recently discovered rs12979860 T/C polymorphism upstream of the IL-28B gene.
In general IL-29 serum levels exceeded IL-28A/B at least twofold, with IL-29 and IL-28A/B levels being significantly higher in carriers of the rs12979860 C allele than in TT homozygous individuals (p<0.02). IL-29 levels were substantially lower in patients with chronic hepatitis C than in healthy controls (p=0.005) and patients with spontaneously resolved hepatitis (p=0.001). Patients with acute hepatitis C showed IL-29 levels intermediate between chronic hepatitis C and normal controls; and IL-29 serum levels were higher in patients who spontaneously resolved hepatitis C than in those who became chronic. In vitro HCV proteins NS3 and E2 directly inhibited IL-29 production in poly I:C-stimulated purified DCs.
Our data suggest that HCV proteins modify IFN-lambda production in DCs. Carriers of the rs12979860 C allele associated with resolution of HCV infection exhibited increased IFN-lambda levels. Moreover, high IFN-lambda levels predisposed to spontaneous resolution of HCV infection. Thus, IFN-lambdas seem to play an important role in the control of hepatitis C.
树突状细胞（DC）可引发适应性免疫应答，是抗病毒细胞因子的重要来源。在丙型肝炎病毒（HCV）感染中，DC 的功能明显受损。迄今为止，研究主要集中在 I 型和 II 型干扰素（IFN）上。我们研究了具有不同 HCV 感染结局患者的血清 IFN-λ1（IL-29）和 IFN-λ2/3（IL-28A/B）水平。
通过分别检测 IL-29 或 IL-28A 和 IL-28B 的 ELISA 法来测量 IFN-λs。结果根据最近发现的 IL-28B 基因上游 rs12979860T/C 多态性进行分层。
通常情况下，IL-29 血清水平至少是 IL-28A/B 的两倍，rs12979860 C 等位基因携带者的 IL-29 和 IL-28A/B 水平明显高于 TT 纯合子个体（p<0.02）。慢性丙型肝炎患者的 IL-29 水平明显低于健康对照者（p=0.005）和自发性肝炎缓解者（p=0.001）。急性丙型肝炎患者的 IL-29 水平介于慢性丙型肝炎和正常对照组之间；自发性丙型肝炎缓解患者的 IL-29 血清水平高于慢性丙型肝炎患者。HCV 蛋白 NS3 和 E2 在 poly I:C 刺激的纯化 DC 中直接抑制 IL-29 的产生。
我们的数据表明，HCV 蛋白修饰了 DC 中的 IFN-λ 产生。与 HCV 感染清除相关的 rs12979860 C 等位基因携带者表现出更高的 IFN-λ 水平。此外，高水平的 IFN-λ 易导致 HCV 感染的自发性缓解。因此，IFN-λs 在控制丙型肝炎中似乎发挥着重要作用。
