Shapiro S, Gershtein V, Elias N, Zuckerman E, Salman N, Lahat N
Immunology Research Unit, Lady Davis Carmel Medical Centre, Haifa, Israel.
Clin Exp Immunol. 1998 Oct;114(1):55-60. doi: 10.1046/j.1365-2249.1998.00693.x.
Natural immune responses, both cellular and humoral, are not capable of terminating HCV infection in most patients. A role has been suggested for peripheral blood leucocytes (PBL) in viral persistence and clinical implications, as these cells may serve as a viral reservoir and at the same time may be inadequate active participants in antiviral immune reactions. IFN-alpha administration, although only partially successful, is currently the main therapy available for chronic HCV patients. In addition to its antiviral effects, IFN-alpha regulates the function of cytokines, their receptors and other molecules of immune importance. The aim of this study was to determine cytokine mRNA expression in PBL derived from chronic HCV patients prior to and at termination of IFN-alpha treatment. HCV RNA was still observed in sera of most patients (10 out of 14 treated patients) at termination of treatment. In pretreated patients mRNA expression of Th2 (IL-4, IL-6 and IL-10) and Th3 (transforming growth factor-beta (TGF-beta)) was observed in only a low percentage of PBL samples from patients, similar to controls. IFN-alpha treatment led to an elevation in the number of samples expressing these cytokines (significant for IL-4, IL-6, IL-10, tumour necrosis factor-alpha (TNF-alpha) and TGF-beta), accompanied by reduction in liver enzymes but in serum viral load in only approximately 30% of patients. Expression of TNF-alpha and TNF-beta mRNA was observed in samples from patients but not controls, while no differences were observed for mRNA of classical Th1 cytokines (IL-2 and IFN-gamma) between patients before or during treatment as well as controls. The cytokine mRNA profile following IFN-alpha treatment points to an anti-inflammatory response which does not appear to be involved in termination of the viral infection. The PBL cytokine profile observed in this study may explain the failure of the immune system to eradicate HCV chronic infection and suggests that early treatment in the acute phase of disease with agents that stimulate cytotoxic immune type 1 responses may lead to eradication of HCV infection.
无论是细胞免疫反应还是体液免疫反应，自然免疫应答在大多数患者中都无法终止丙型肝炎病毒（HCV）感染。外周血白细胞（PBL）在病毒持续存在及临床影响方面的作用已被提及，因为这些细胞可能充当病毒储存库，同时在抗病毒免疫反应中可能并非充分的积极参与者。α干扰素给药目前是慢性HCV患者可用的主要治疗方法，尽管仅部分成功。除了其抗病毒作用外，α干扰素还调节细胞因子及其受体以及其他具有免疫重要性的分子的功能。本研究的目的是确定慢性HCV患者在α干扰素治疗前及治疗结束时PBL中细胞因子mRNA的表达情况。治疗结束时，大多数患者（14例接受治疗的患者中有10例）血清中仍可检测到HCV RNA。在预处理患者中，与对照组相似，仅在低比例的患者PBL样本中观察到Th2（IL-4、IL-6和IL-10）和Th3（转化生长因子-β（TGF-β））的mRNA表达。α干扰素治疗导致表达这些细胞因子的样本数量增加（IL-4、IL-6、IL-10、肿瘤坏死因子-α（TNF-α）和TGF-β有显著变化），同时伴有肝酶降低，但仅约30%的患者血清病毒载量降低。在患者样本中观察到TNF-α和TNF-β mRNA的表达，而对照组未观察到，同时在治疗前或治疗期间的患者以及对照组之间，经典Th1细胞因子（IL-2和IFN-γ）的mRNA未观察到差异。α干扰素治疗后的细胞因子mRNA谱表明存在抗炎反应，这似乎与病毒感染的终止无关。本研究中观察到的PBL细胞因子谱可能解释了免疫系统无法根除HCV慢性感染的原因，并表明在疾病急性期早期用刺激细胞毒性1型免疫反应的药物进行治疗可能导致HCV感染的根除。
