{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T10:09:09Z","timestamp":1773310149690,"version":"3.50.1"},"reference-count":42,"publisher":"Proceedings of the National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,7,19]]},"abstract":"<jats:p>\n                    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: (\n                    <jats:italic>i<\/jats:italic>\n                    ) antiviral drugs exert selective pressure on the virus, resulting in the generation of more fit viral progeny that are resistant to treatment; and (\n                    <jats:italic>ii<\/jats:italic>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1107024108","type":"journal-article","created":{"date-parts":[[2011,6,29]],"date-time":"2011-06-29T23:34:04Z","timestamp":1309390444000},"page":"12018-12023","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":210,"title":["Suppression of cytokine storm with a sphingosine analog provides protection against pathogenic influenza virus"],"prefix":"10.1073","volume":"108","author":[{"given":"Kevin B.","family":"Walsh","sequence":"first","affiliation":[{"name":"Departments of aImmunology and Microbial Science and"}]},{"given":"John R.","family":"Teijaro","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and Microbial Science and"}]},{"given":"Peter R.","family":"Wilker","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706;"}]},{"given":"Anna","family":"Jatzek","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706;"}]},{"given":"Daniel M.","family":"Fremgen","sequence":"additional","affiliation":[{"name":"Departments of aImmunology and Microbial Science and"}]},{"given":"Subash C.","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706;"}]},{"given":"Tokiko","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Exploratory Research for Advanced Technology Infection-Induced Host-Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan;"}]},{"given":"Masato","family":"Hatta","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706;"}]},{"given":"Kyoko","family":"Shinya","sequence":"additional","affiliation":[{"name":"Division of Zoonosis, Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Hyogo, Japan; and"}]},{"given":"Marulasiddappa","family":"Suresh","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706;"}]},{"given":"Yoshihiro","family":"Kawaoka","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, University of Wisconsin, Madison, WI 53706;"},{"name":"Exploratory Research for Advanced Technology Infection-Induced Host-Responses Project, Japan Science and Technology Agency, Saitama 332-0012, Japan;"},{"name":"Division of Zoonosis, Department of Microbiology and Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Hyogo, Japan; and"},{"name":"International Research Center for Infectious Diseases, Institute of Medical Science, and"},{"name":"Division of Virology, Department of Microbiology and Immunology, University of Tokyo, Tokyo 108-8639, Japan"}]},{"given":"Hugh","family":"Rosen","sequence":"additional","affiliation":[{"name":"Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037;"}]},{"given":"Michael B. 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