Open AccessSuppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus
Author(s) -
Kevin B. Walsh,
John R. Teijaro,
Peter R. Wilker,
Anna Jatzek,
Daniel Fremgen,
Subash C. Das,
Tokiko Watanabe,
Masato Hatta,
Kyoko Shinya,
M. Suresh,
Yoshihiro Kawaoka,
Hugh Rosen,
Michael B. A. Oldstone
Publication year - 2011
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1107024108
Subject(s) - cytokine storm , virus , oseltamivir , virology , viral replication , immune system , influenza a virus , neuraminidase , immunology , cytokine , chemokine , antiviral drug , biology , medicine , disease , infectious disease (medical specialty) , covid-19 , pathology
Human pandemic H1N1 2009 influenza virus rapidly infected millions worldwide and was associated with significant mortality. Antiviral drugs that inhibit influenza virus replication are the primary therapy used to diminish disease; however, there are two significant limitations to their effective use: (i ) antiviral drugs exert selective pressure on the virus, resulting in the generation of more fit viral progeny that are resistant to treatment; and (ii ) antiviral drugs do not directly inhibit immune-mediated pulmonary injury that is a significant component of disease. Here we show that dampening the host's immune response against influenza virus using an immunomodulatory drug, AAL-R, provides significant protection from mortality (82%) over that of the neuraminidase inhibitor oseltamivir alone (50%). AAL-R combined with oseltamivir provided maximum protection against a lethal challenge of influenza virus (96%). Mechanistically, AAL-R inhibits cellular and cytokine/chemokine responses to limit immunopathologic damage, while maintaining host control of virus replication. With cytokine storm playing a role in the pathogenesis of a wide assortment of viral, bacterial, and immunologic diseases, a therapeutic approach using sphingosine analogs is of particular interest.