B, ntiviral and anti-inflammatory activity of arbidol hydrochloride in influenza A （HIN1） virus infection

• Published in: 中国药理学报：英文版 no. 8; pp. 1075 - 1083
• Main Author: Qiang LIU Hai-rong XIONG Li LU Yuan-yuan LIU Fan LUO Wei HOU Zhan-qiu YANG
• Format: Journal Article
• Language: English
• Published: 2013
• Subjects: IL-12; 实时定量RT-PCR; 抗炎活性; 流感病毒; 炎性细胞因子; 病毒感染; 盐酸; 神经氨酸酶抑制剂
• ISSN: 1671-4083; 1745-7254

Aim： To investigate the effects of arbidol hydrochloride （ARB）, a widely used antiviral agent, on the inflammation Jnduced by influenza virus. Methods： MDCK cells were infected with seasonal influenza A/FM/1/47 （HIN1） or pandemic influenza A/Hubei/71/2009 （HIN1）. In vitro cytotoxicity and antiviral activity of ARB was determined using MTT assay. BALB/c mice were infected with A/FM/1/47 （HIN1）. Four hours later the mice were administered ARB （45, 90, and 180 mg.kg-1〈1-1） or the neuraminidase inhibitor oseltamivir （22.5 mg.kg-1〈1-1） via oral gavage once a day for 5 d. Body-weight, median survival time, viral titer, and lung index of the mice were measured. The levels of inflammatory cytokines were examined using real-time RT-PCR and ELISA. Results： Both HIN1 stains were equally sensitive to ARB as tested in vitro. In the infected mice, ARB （90 and 180 mg.kg-1.d-1） significantly decreased the mortality, alleviated virus-induced lung lesions and viral titers. Furthermore, ARB suppressed the levels of IL-1β, IL-6, IL-12, and TNF-a, and elevated the level of IL-IO in the bronchoalveolar lavage fluids and lung tissues. However, ARB did not significantly affect the levels of IFN-a and IFN-γ, but reduced the level of IFN-β1 in lung tissues at 5 dpi. In peritoneal macrophages challenged with A/FM/1/47 （HIN1） or poly hC, ARB （20 pmol/L） suppressed the levels of IL-1β, IL-6, IL-12, and TNF-a, and elevated the level of IL-IO. Oseltamivir produced comparable alleviation of virus-induced lung lesions with more reduction in the viral titers, but less effective modulation of the inflammatory cytokines. Conclusion： ARB efficiently inhibits both HIN1 stains and diminishes both viral replication and acute inflammation through modulating the expression of inflammatory cytokines.