Libra Massimo, Mangano Katia, Anzaldi Massimiliano, Quattrocchi Cinzia, Donia Marco, di Marco Roberto, Signorelli Santo, Scalia Guido, Zignego Anna L, de Re Valli, Mazzarino Maria C, Nicoletti Ferdinando
Department of Biomedical Sciences, University of Catania, 95124 Catania, Italy.
Oncol Rep. 2006 May;15(5):1305-8.
Hepatitis C virus (HCV) causes hepatitis, liver cirrhosis and hepatocellular carcinoma, and may also induce type II mixed cryoglobulinemia syndrome (MC), a disease characterized by clonal B-cell lymphoproliferations that can evolve into non-Hodgkin's lymphoma (NHL). Interleukin-1 (IL-1) is a cytokine that plays an important role in initiating the cascade of events of immunoinflammatory responses through costimulation of T lymphocytes, B-cell proliferation, induction of adhesion molecules and stimulation of the production of other inflammatory cytokines. The role of IL-1 in immunoinflammatory responses is highlighted by the presence of endogenous regulators (IL-1 receptor antagonist, soluble receptors type 1 and II, human IL-1 accessory protein) that, when secreted into the blood stream may serve as endogenous regulators of IL-1 action. The aim of this study was to evaluate whether abnormalities in the blood levels of IL-1beta IL-1 receptor antagonist, soluble IL-1 receptor type II and human IL-1 accessory protein in HCV+ patients are associated with development of MC and/or NHL. Relative to healthy controls, we observed: i) an increase in the circulating levels of IL-1beta in HCV+ patients simultaneously affected by NHL; ii) increased levels of IL-1 accessory protein in patients singly infected by HCV; iii) increase of IL-1 receptor antagonist in HCV+ patients and in those affected also by NHL with or without MC; iv) a homogeneous increase of sIL-1R type II in all the subgroup of patients. These data indicate that an attempt to increased circulating levels of IL-1 inhibitors occurs at different extent in the course of HCV infection as well as in its progression to NHL and/or MC.
丙型肝炎病毒（HCV）可导致肝炎、肝硬化和肝细胞癌，还可能诱发II型混合性冷球蛋白血症综合征（MC），这是一种以克隆性B细胞淋巴增殖为特征的疾病，可发展为非霍奇金淋巴瘤（NHL）。白细胞介素-1（IL-1）是一种细胞因子，通过共刺激T淋巴细胞、B细胞增殖、诱导黏附分子以及刺激其他炎性细胞因子的产生，在启动免疫炎症反应的级联事件中发挥重要作用。内源性调节因子（IL-1受体拮抗剂、可溶性I型和II型受体、人IL-1辅助蛋白）的存在突出了IL-1在免疫炎症反应中的作用，这些调节因子分泌到血流中时可作为IL-1作用的内源性调节因子。本研究的目的是评估HCV阳性患者血液中IL-1β、IL-1受体拮抗剂、可溶性II型IL-1受体和人IL-1辅助蛋白水平的异常是否与MC和/或NHL的发生有关。相对于健康对照，我们观察到：i）同时患有NHL的HCV阳性患者循环中IL-1β水平升高；ii）单独感染HCV的患者中IL-1辅助蛋白水平升高；iii）HCV阳性患者以及患有或未患有MC的NHL患者中IL-1受体拮抗剂增加；iv）所有患者亚组中可溶性II型IL-1受体均均匀增加。这些数据表明，在HCV感染过程及其发展为NHL和/或MC的过程中，不同程度地会出现IL-1抑制剂循环水平升高的情况。
