title: Cytokine storm plays a direct role in the morbidity and mortality from influenza virus infection and is chemically treatable with a single sphingosine-1-phosphate agonist molecule.
abstract: Cytokine storm defines a dysregulation of and an excessively exaggerated immune response most often accompanying selected viral infections and several autoimmune diseases. Newly emerging and re-emerging infections of the respiratory tract, especially influenza, SARS, and hantavirus post considerable medical problems. Their morbidities and mortalities are often a direct result of cytokine storm. This chapter visits primarily influenza virus infection and resultant cytokine storm. It provides the compelling evidence that illuminates cytokine storm in influenza pathogenesis and the clear findings that cytokine storm is chemically tractable by therapy directed toward sphingosine-1-phosphate receptor (S1PR) modulation, specifically S1P1R agonist therapy. The mechanism(s) of how S1P1R signaling works and the pathways involved are subjects of this review.
authors.affiliation: Department of Immunology and Microbial Science, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA, 92037, USA, mbaobo@scripps.edu.
authors.forename: Michael B A
authors.initials: MB
authors.lastname: Oldstone
authors.forename: Hugh
authors.initials: H
authors.lastname: Rosen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D007251:Influenza, Human / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality* / Q000821:virology; D008246:Lysophospholipids / Q000819:agonists* / Q000627:therapeutic use*; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000276:immunology; D013110:Sphingosine / Q000819:agonists / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D016207:Cytokines; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; D013110:Sphingosine
references.citation: PLoS One. 2012;7(1):e29347
references.pmid: 22235288
references.citation: Respir Physiol Neurobiol. 2011 Jan 31;175(1):185-7
references.pmid: 21075220
references.citation: Nat Chem Biol. 2011 May;7(5):254-6
references.pmid: 21445057
references.citation: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1560-5
references.pmid: 19164548
references.citation: PLoS One. 2010 Oct 01;5(10):
references.pmid: 20957032
references.citation: Immunity. 2007 Aug;27(2):240-52
references.pmid: 17723216
references.citation: Lancet Infect Dis. 2012 Sep;12(9):687-95
references.pmid: 22738893
references.citation: Annu Rev Biochem. 2009;78:743-68
references.pmid: 19231986
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000604
references.pmid: 19798428
references.citation: Bull Hist Med. 2002 Spring;76(1):105-15
references.pmid: 11875246
references.citation: Proc Natl Acad Sci U S A. 2009 Mar 3;106(9):3455-60
references.pmid: 19218453
references.citation: Annu Rev Biochem. 2013;82:637-62
references.pmid: 23527695
references.citation: Nat Immunol. 2007 Nov;8(11):1188-93
references.pmid: 17952044
references.citation: Antivir Ther. 2012;17(1 Pt B):159-73
references.pmid: 22311680
references.citation: Virology. 2014 Mar;452-453:152-7
references.pmid: 24606692
references.citation: J Virol. 2011 Nov;85(21):11208-19
references.pmid: 21865394
references.citation: PLoS One. 2011;6(10):e26050
references.pmid: 22022504
references.citation: Proc Natl Acad Sci U S A. 2011 Jul 19;108(29):12018-23
references.pmid: 21715659
references.citation: Mol Pharmacol. 2008 Sep;74(3):896-903
references.pmid: 18577684
references.citation: Cell. 2011 Sep 16;146(6):980-91
references.pmid: 21925319
references.citation: Nat Med. 2006 Oct;12(10):1203-7
references.pmid: 16964257
references.citation: PLoS One. 2011 Jan 06;6(1):e16028
references.pmid: 21253602
references.citation: Trends Immunol. 2007 Mar;28(3):102-7
references.pmid: 17276731
references.citation: Proc Natl Acad Sci U S A. 2010 Nov 16;107(46):19973-8
references.pmid: 21045126
references.citation: Nature. 2007 Jan 18;445(7125):319-23
references.pmid: 17230189
references.citation: Infect Disord Drug Targets. 2007 Dec;7(4):336-43
references.pmid: 18220965