Inhibition of the cytokine response does not protect against lethal H5N1 influenza infection
Published online before print July 17, 2007,
PNAS | July 24, 2007
Freely available online through the PNAS open access option.
pnas.org
Rachelle Salomon*, Erich Hoffmann*, and Robert G. Webster*,{dagger},{ddagger}
*Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105-2794; and {dagger}Department of Pathology, University of Tennessee, Memphis, TN 38105
Contributed by Robert G. Webster, June 5, 2007 (received for review March 29, 2007)
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-{alpha}, 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.
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.
The authors declare no conflict of interest.
{ddagger}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@stjude.org
© 2007 by The National Academy of Sciences of the USA |
