Antiviral and anti-inflammatory activity of arbidol hydrochloride in influenza A (H1N1) virus infection

Aim: To investigate the effects of arbidol hydrochloride (ARB), a widely used antiviral agent, on the inflammation induced by influenza virus. Methods: MDCK cells were infected with seasonal influenza A/FM/1/47 (H1N1) or pandemic influenza A/Hubei/71/2009 (H1N1). In vitro cytotoxicity and antiviral activity of ARB was determined using MTT assay. Balb/c mice were infected with A/FM/1/47 (H1N1). Four hours later the mice were administered ARB (45, 90, and 180 mg.kg(-1).d(-1)) or the neuraminidase inhibitor oseltamivir (22.5 mg.kg(-1).d(-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 H1N1 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-1 beta, IL-6, IL-12, and TNF-alpha, and elevated the level of IL-10 in the bronchoalveolar lavage fluids and lung tissues. However, ARB did not significantly affect the levels of IFN-alpha and IFN-gamma, but reduced the level of IFN-beta 1 in lung tissues at 5 dpi. In peritoneal macrophages challenged with A/FM/1/47 (H1N1) or poly I:C, ARB (20 mu mol/L) suppressed the levels of IL-1 beta, IL-6, IL-12, and TNF-alpha, and elevated the level of IL-10. 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 H1N1 stains and diminishes both viral replication and acute inflammation through modulating the expression of inflammatory cytokines.