Corrado A, Mazzi V, Ferrari S M, Politti U, Giuggioli D, Antonelli A, Fallahi P, Ferri C
Dipartimento di Medicina Clinica e Sperimentale, Università di Pis.
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto, Università di Modena e Reggio Emilia, Modena, Italia.
Clin Ter. 2014;165(4):e317-22. doi: 10.7417/CT.2014.1749.
IFN-γ-induced protein 10 (IP-10) and its receptor, CXCR3 chemokine (C-X-C motif) receptor 3 (CXCR3), appear to contribute to the pathogenesis of HCV related mixed cryoglobulinemia (HCV+MC). The secretion of IP-10 by CD4+, CD8+ and natural killer (NK)-T cells is dependent on interferon (IFN)-γ, which is itself mediated by the interleukin (IL)-12 cytokine family. Under the influence of IFN-γ, IP-10 is secreted by several cell types including lymphocytes, hepatocytes, endothelial cells, fibroblasts, etc. In tissues, recruited T helper (Th) 1 lymphocytes may be responsible for enhanced IFN-γ and tumor necrosis factor (TNF)-α production, which in turn stimulates IP-10 secretion from the cells, therefore creating an amplification feedback loop, and perpetuating the autoimmune process. High levels circulation of IP-10 have been found in HCV+MC, especially in patients with clinically active vasculitis. Furthermore, HCV+MC patients with autoimmune thyroiditis (AT), have higher levels than those without AT. Further studies are needed to investigate interactions between chemokines and cytokines in the pathogenesis, and to evaluate whether IP-10 is a novel therapeutic target in HCV+MC.
干扰素-γ诱导蛋白10（IP-10）及其受体CXC趋化因子受体3（CXCR3）似乎在丙型肝炎病毒相关混合性冷球蛋白血症（HCV+MC）的发病机制中发挥作用。CD4+、CD8+和自然杀伤（NK）-T细胞分泌IP-10依赖于干扰素（IFN）-γ，而IFN-γ本身由白细胞介素（IL）-12细胞因子家族介导。在IFN-γ的影响下，包括淋巴细胞、肝细胞、内皮细胞、成纤维细胞等多种细胞类型都会分泌IP-10。在组织中，募集到的辅助性T（Th）1淋巴细胞可能导致IFN-γ和肿瘤坏死因子（TNF）-α产生增加，进而刺激细胞分泌IP-10，从而形成一个放大的反馈回路，使自身免疫过程持续存在。在HCV+MC患者中，尤其是临床有活动性血管炎的患者，已发现IP-10的循环水平较高。此外，患有自身免疫性甲状腺炎（AT）的HCV+MC患者，其IP-10水平高于无AT的患者。还需要进一步研究来探讨趋化因子和细胞因子在发病机制中的相互作用，并评估IP-10是否是HCV+MC的一个新的治疗靶点。
