Forcina Gabriele, D'Ettorre Gabriella, Mastroianni Claudio M, Carnevalini Martina, Scorzolini Laura, Ceccarelli Giancarlo, D'Agostino Claudia, Lichtner Miriam, Massetti Anna P, Vullo Vincenzo
Department of Infectious and Tropical Diseases, La Sapienza University, Policlinico Umberto I, Viale Regina Elena 331, 00161 Rome, Italy.
Cytokine. 2004 Mar 21;25(6):283-90. doi: 10.1016/j.cyto.2003.12.004.
Interleukin (IL)-15 is a cytokine that has lymphocyte stimulatory activity similar to that of IL-2, and plays important immunoregulatory functions during HIV disease. To evaluate the role of IL-15 in HIV infection the following patients were studied: 18 antiretroviral-naive patients with advanced disease; 19 patients with continuous viral suppression and immunological response after 48-120 weeks of highly active antiretroviral therapy (HAART); and 12 patients with evidence of virological and immunological HAART treatment failure. Nineteen healthy blood donors were included as controls. The production of IL-15 by human peripheral blood monocytes stimulated with lipopolysaccharide and Mycobacterium avium complex, the priming effect of IL-15 on IFN-gamma production from purified CD4(+) and CD8(+) T cells, and the ability of IL-15 to stimulate the beta-chemokine release from purified CD4(+) and CD8(+) T cells were analyzed. In the present work IL-15 production by human peripheral blood monocytes was significantly increased in HIV-infected patients with long-term virological and immunological response to HAART. IL-15 enhanced the in vitro priming of CD4(+) and CD8(+) T cells for IFN-gamma production, also in patients receiving HAART. Finally, IL-15 had positive effects on RANTES, MIP-1alpha, and MIP-1beta release by CD4(+) and CD8(+) T cells. In conclusion IL-15 could affect the immune response of HIV-infected patients by augmenting and/or modulating IFN-gamma production and beta-chemokine release. These data about functional properties of IL-15 could provide new implications for immune-based therapies in HIV infection.
白细胞介素(IL)-15是一种细胞因子,具有与IL-2相似的淋巴细胞刺激活性,在HIV疾病期间发挥重要的免疫调节功能。为了评估IL-15在HIV感染中的作用,对以下患者进行了研究:18例初治的晚期疾病患者;19例在接受48 - 120周高效抗逆转录病毒治疗(HAART)后实现持续病毒抑制和免疫反应的患者;以及12例有病毒学和免疫学HAART治疗失败证据的患者。纳入19名健康献血者作为对照。分析了用脂多糖和鸟分枝杆菌复合物刺激的人外周血单核细胞产生IL-15的情况、IL-15对纯化的CD4(+)和CD8(+) T细胞产生IFN-γ的启动作用,以及IL-15刺激纯化的CD4(+)和CD8(+) T细胞释放β趋化因子的能力。在本研究中,对HAART有长期病毒学和免疫反应的HIV感染患者,其外周血单核细胞产生IL-15的水平显著增加。IL-15增强了CD4(+)和CD8(+) T细胞体外产生IFN-γ的启动作用,接受HAART治疗的患者也是如此。最后,IL-15对CD4(+)和CD8(+) T细胞释放RANTES、MIP-1α和MIP-1β有积极作用。总之,IL-15可能通过增强和/或调节IFN-γ的产生以及β趋化因子的释放来影响HIV感染患者的免疫反应。这些关于IL-15功能特性的数据可能为HIV感染的免疫治疗提供新的启示。