Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection
- *Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-2794; and
- †Department of Pathology, University of Tennessee, Memphis, TN 38105
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Contributed by Robert G. Webster, June 5, 2007 (received for review March 29, 2007)
Abstract
Because proinflammatory cytokines are markedly elevated during H5N1 influenza virus infection, the “cytokine storm” is hypothesized to be the main cause of mortality. Here, we demonstrate that mice deficient in the hallmark inflammatory cytokines TNF-α, IL-6, or CC chemokine ligand 2 succumb to infection with A/Vietnam/1203/04 (H5N1) virus, as do wild-type mice treated with glucocorticoids for suppression of cytokines. Because cytokine inhibition does not protect against death, therapies that target the virus rather than cytokines may be preferable.
Footnotes
- ‡To whom correspondence should be addressed at: Department of Infectious Diseases, St. Jude Children's Research Hospital, 332 North Lauderdale, Memphis, TN 38105-2794. E-mail: robert.webster{at}stjude.org
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Author contributions: R.S., E.H., and R.G.W. designed research; R.S. performed research; R.S., E.H., and R.G.W. analyzed data; and R.S., E.H., and R.G.W. wrote the paper.
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The authors declare no conflict of interest.
- Abbreviations:
- CCL2,
- CC chemokine ligand 2;
- TNFR,
- TNF receptor.
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Freely available online through the PNAS open access option.
- © 2007 by The National Academy of Sciences of the USA
