Kitano Mitsutaka, Itoh Yasushi, Ishigaki Hirohito, Nakayama Misako, Ishida Hideaki, Pham Van Loi, Arikata Masahiko, Shichinohe Shintaro, Tsuchiya Hideaki, Kitagawa Naoko, Kobayashi Masanori, Yoshida Ryu, Sato Akihiko, Le Quynh Mai, Kawaoka Yoshihiro, Ogasawara Kazumasa
Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan Infectious Diseases, Medicinal Research Laboratories, Shionogi & Co., Ltd., Osaka, Japan.
Department of Pathology, Shiga University of Medical Science, Otsu, Shiga, Japan
Antimicrob Agents Chemother. 2014 Aug;58(8):4795-803. doi: 10.1128/AAC.02817-14. Epub 2014 Jun 9.
Highly pathogenic avian influenza A (H5N1) viruses cause severe and often fatal disease in humans. We evaluated the efficacy of repeated intravenous dosing of the neuraminidase inhibitor peramivir against highly pathogenic avian influenza virus A/Vietnam/UT3040/2004 (H5N1) infection in cynomolgus macaques. Repeated dosing of peramivir (30 mg/kg/day once a day for 5 days) starting immediately after infection significantly reduced viral titers in the upper respiratory tract, body weight loss, and cytokine production and resulted in a significant body temperature reduction in infected macaques compared with that of macaques administered a vehicle (P < 0.05). Repeated administration of peramivir starting at 24 h after infection also resulted in a reduction in viral titers and a reduction in the period of virus detection in the upper respiratory tract, although the body temperature change was not statistically significant. The macaque model used in the present study demonstrated that inhibition of viral replication at an early time point after infection by repeated intravenous treatment with peramivir is critical for reduction of the production of cytokines, i.e., interleukin-6 (IL-6), tumor necrosis factor α, gamma interferon, monocyte chemotactic protein 1, and IL-12p40, resulting in amelioration of symptoms caused by highly pathogenic avian influenza virus infection.
高致病性甲型禽流感（H5N1）病毒可导致人类患上严重且往往致命的疾病。我们评估了对食蟹猴重复静脉注射神经氨酸酶抑制剂帕拉米韦，以对抗高致病性甲型禽流感病毒A/越南/UT3040/2004（H5N1）感染的效果。感染后立即开始重复注射帕拉米韦（30毫克/千克/天，每天一次，共5天），与注射赋形剂的食蟹猴相比，显著降低了上呼吸道中的病毒滴度、体重减轻和细胞因子产生，并使受感染食蟹猴的体温显著降低（P < 0.05）。感染后24小时开始重复注射帕拉米韦，也导致病毒滴度降低以及上呼吸道中病毒检测期缩短，尽管体温变化无统计学意义。本研究中使用的食蟹猴模型表明，感染后早期通过帕拉米韦重复静脉治疗抑制病毒复制，对于减少细胞因子即白细胞介素-6（IL-6）、肿瘤坏死因子α、γ干扰素、单核细胞趋化蛋白1和IL-12p40的产生至关重要，从而改善高致病性禽流感病毒感染引起的症状。
