Pugliese Agostino, Gennero Luisa, Vidotto Valerio, Speranza Filippo, Tambini Roberto, Torre Donato
Department of Medical and Surgical Sciences, Section of Clinical Microbiology, Amedeo di Savoia Hospital, University of Turin, Corso Svizzera 164-20249 Turin, Italy.
Cell Biochem Funct. 2002 Dec;20(4):333-7. doi: 10.1002/cbf.981.
Interleukin-18 (IL-18) is a recently identified immunoregulatory cytokine expressed by activated macrophages, that induces production of interferon-gamma (IFN-gamma) and Th-1 development. Recently some investigators reported controversial in vitro data on IL-18 stimulation of HIV-1 replication in several cell lines. In the present study the effect of IL-18 on HIV replication in a human chronically HIV-1-infected lymphocytic T cell line (H9-V) was investigated. HIV-1 replication was determined by an immunoassay method in order to evaluate the content of p24 antigen in the cell culture supernatants. Stimulation of H9-V cells with IL-18 resulted in increased production of p24, especially at concentrations of 0.01 microg ml(-1) and 0.10 microg ml(-1). Moreover a significant and persistent IL-18 stimulation of HIV-1 replication was observed at a concentration of 0.01 microg ml(-1) during a 7-day period. Pre-treatment of IL-18 with a specific neutralizing monoclonal antibody significantly reduced HIV-1 replication. These experiments show that IL-18 promotes the increase of HIV-1 replication in human chronically-infected lymphocytic T cells and confirm the role of IL-18 as a proimflammatory cytokine in stimulating and maintaining HIV-1 replication during the course of the disease. In a successive set of experiments, since one of the main activities of IL-18 is the induction of IFN-gamma, we evaluated the effect of this biological modifier on H9-V cells. In particular, IFN-gamma shows a significant effect on cell replication and on reduction of CD4 and CD71 surface expression.
白细胞介素-18（IL-18）是一种最近发现的免疫调节细胞因子，由活化的巨噬细胞表达，可诱导γ干扰素（IFN-γ）的产生和Th-1细胞的发育。最近，一些研究人员报告了关于IL-18在几种细胞系中刺激HIV-1复制的有争议的体外数据。在本研究中，研究了IL-18对人慢性HIV-1感染的淋巴细胞T细胞系（H9-V）中HIV复制的影响。通过免疫测定法测定HIV-1复制，以评估细胞培养上清液中p24抗原的含量。用IL-18刺激H9-V细胞导致p24产生增加，尤其是在浓度为0.01μg/ml和0.10μg/ml时。此外，在7天期间，在浓度为0.01μg/ml时观察到IL-18对HIV-1复制有显著且持续的刺激作用。用特异性中和单克隆抗体预处理IL-18可显著降低HIV-1复制。这些实验表明，IL-18促进人慢性感染淋巴细胞T细胞中HIV-1复制的增加，并证实了IL-18作为促炎细胞因子在疾病过程中刺激和维持HIV-1复制中的作用。在随后的一组实验中，由于IL-18的主要活性之一是诱导IFN-γ，我们评估了这种生物修饰剂对H9-V细胞的影响。特别是，IFN-γ对细胞复制以及CD4和CD71表面表达的降低有显著影响。
