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Influenza and Inflammation — A Lethal Link
Virulence of the H5N1 and the 1918–1919 pandemic influenza A viruses has been linked to induction of host inflammatory responses.
The potential for a human H5N1 influenza pandemic is a major public health concern. What makes avian-derived H5N1 strains, and the influenza strain underlying the 1918–1919 human pandemic, so virulent remains unclear. Two new studies implicate viral triggering of cytokine-mediated lung inflammation.
Kash and colleagues infected mice with a contemporary human influenza A H1N1 virus or with the same virus in which they had introduced an increasing number of genes derived from the 1918–1919 pandemic strain. Mice infected with a virus containing all eight genes from the pandemic strain died the fastest and had the highest viral titers at days 1 and 3. As the number of genes from the 1918 strain increased, so did the degree of neutrophilic inflammatory response in the lung and the extent to which death receptor, interleukin (IL)-6, type I interferon, and Toll-like receptor responses were activated.
De Jong and colleagues conducted virologic and immunologic analyses of respiratory and nonrespiratory samples from 18 individuals infected with H5N1 avian influenza (13 of whom died) and 8 patients hospitalized during the same period with H3N2 or H1N1 human influenza. Among H5N1-infected patients, viral loads were higher in pharyngeal samples than in nasal samples; titers were highest in the patients who died. Viral RNA was also detected in the blood from 9 of 16 H5N1-infected patients (all fatal cases), but 0 of 6 control patients. H5N1 infection was associated with activation of monocyte/macrophage chemoattractants (IP-10, MIG, and MCP-1), elevated levels of the neutrophil chemoattractant IL-8 in lung tissue, and higher plasma levels of IL-10, IL-6 and interferon-
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Comment: The extent of the host inflammatory response triggered by various influenza strains was strongly correlated with influenza virulence. The sum of all influenza A gene products, rather than any single gene product, may well determine the degree of this response. Development of pharmacologic or immunologic means to limit such response could be key to reducing morbidity and mortality in the event of an H5N1 influenza pandemic.
— Bradley E. Britigan, MD
Published in Journal Watch Infectious Diseases October 25, 2006
Citation(s):
de Jong MD et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercytokinemia. Nat Med 2006 Oct; 12:1203-7.
- Medline abstract (Free)
Kash JC et al. Genomic analysis of increased host immune and cell death responses induced by 1918 influenza virus. Nature 2006 Oct 5; 443:578-81.
- Medline abstract (Free)
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