Abstract
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-1β, IL-6, IL-12, and TNF-α, 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-α 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 (H1N1) or poly I:C, ARB (20 μmol/L) suppressed the levels of IL-1β, IL-6, IL-12, and TNF-α, 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.
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Acknowledgements
This work was supported by the National Mega Project on Major Drug Development (2009ZX09301-014-1), the National Natural Science Foundation of China (No 30873104 and 81000734) and the Fundamental Research Funds for the Central Universities (4101045).
We thank Prof Tian-xian LI for the viruses. We gratefully acknowledge all individuals within the ABSL-3 team for their kindness and their technical help.
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Liu, Q., Xiong, Hr., Lu, L. et al. Antiviral and anti-inflammatory activity of arbidol hydrochloride in influenza A (H1N1) virus infection. Acta Pharmacol Sin 34, 1075–1083 (2013). https://doi.org/10.1038/aps.2013.54
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DOI: https://doi.org/10.1038/aps.2013.54
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