Kanda T, Tanaka T, Sekiguchi K, Seta Y, Kurimoto M, Wilson McManus J E, Nagai R, Yang D, McManus B M, Kobayashi I
Department of General Medicine, Gunma University School of Medicine, 3-39-15, Showa-machi, Maebashi, 371, Japan.
J Mol Cell Cardiol. 2000 Dec;32(12):2163-71. doi: 10.1006/jmcc.2000.1242.
Encephalomyocarditis virus causes viral myocarditis with myocyte necrosis and inflammatory cell infiltration in mice. Because previous studies have shown that some cytokines prevent the sequelae of myocarditis, we assessed the effect of a newly identified cytokine, interleukin-18 (IL-18), in preventing the sequelae of myocarditis. Murine IL-18 (10 microg/day/mouse) was given peritoneally for 10 days in C3H mice infected with EMC virus. Mice were divided into group IL-18 (infected-treated), saline group (infected-untreated), group IL-18-2 (treatment started on day 2), group IL-18-5 (treatment started on day 5). Although the 14-day survival rate in saline group was 20%, that in the group IL-18 increased to 80% (P<0.05). Either mice in group IL-18-2 or in group IL-18-5 did not survive longer than saline group. The viral titer of the heart on day 3 was lower in group IL-18 compared to the saline group (1.00+/-0.20 log(10)tissue culture infected dose (TCID)(50)/mg wet weight v 1.42+/-0.12 log(10)TCID(50)/mg, n=3 of each). Mice in group IL-18 had less myocardial necrosis and cellular infiltration than the saline group. The myocardial expression of interferon- gamma (IFN- gamma) mRNA in group IL-18 was significantly (P<0.05) greater than the saline group on days 1 and 3 after viral inoculation. Circulating IFN- gamma was significantly elevated on days 1, 5, and 7, but significantly reduced on day 3. The natural killer cell activities in the spleen on days 1, 3, and 5 were significantly (P<0.05) greater in group IL-18 than in the saline group (41+/-9%v 10+/-6% on day 3, 4 of each). We conclude that IL-18 reduces the severity of EMC viral myocarditis by inducing cardiac expression of IFN- gamma mRNA and increasing splenic natural killer cell activity.
脑心肌炎病毒可在小鼠中引发病毒性心肌炎，伴有心肌细胞坏死和炎性细胞浸润。由于先前的研究表明某些细胞因子可预防心肌炎后遗症，我们评估了一种新发现的细胞因子白细胞介素-18（IL-18）在预防心肌炎后遗症方面的作用。对感染脑心肌炎病毒的C3H小鼠腹腔注射小鼠IL-18（10微克/天/只），持续10天。小鼠被分为IL-18组（感染-治疗组）、生理盐水组（感染-未治疗组）、IL-18-2组（第2天开始治疗）、IL-18-5组（第5天开始治疗）。虽然生理盐水组的14天生存率为20%，但IL-18组的生存率提高到了80%（P<0.05）。IL-18-2组或IL-18-5组的小鼠存活时间均未超过生理盐水组。与生理盐水组相比，IL-18组第3天心脏的病毒滴度较低（1.00±0.20 log(10)组织培养感染剂量（TCID）(50)/毫克湿重对1.42±0.12 log(10)TCID(50)/毫克，每组n = 3）。IL-18组小鼠的心肌坏死和细胞浸润比生理盐水组少。在病毒接种后第1天和第3天，IL-18组心肌中干扰素-γ（IFN-γ）mRNA的表达显著高于生理盐水组（P<0.05）。循环中的IFN-γ在第1天、第5天和第7天显著升高，但在第3天显著降低。在第1天、第3天和第5天，IL-18组脾脏中的自然杀伤细胞活性显著高于生理盐水组（第3天为41±9%对10±6%，每组4只）。我们得出结论，IL-18通过诱导心脏IFN-γ mRNA表达和增加脾脏自然杀伤细胞活性来减轻脑心肌炎病毒心肌炎的严重程度。
