Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents: why they are needed and how they might work
Article first published online: 12 JUN 2009
© 2009 Blackwell Publishing Ltd
Influenza and Other Respiratory Viruses
Volume 3, Issue 4, pages 129–142, July 2009
How to Cite
Fedson, D. S. (2009), Confronting the next influenza pandemic with anti-inflammatory and immunomodulatory agents: why they are needed and how they might work. Influenza and Other Respiratory Viruses, 3: 129–142. doi: 10.1111/j.1750-2659.2009.00090.x
- Issue published online: 15 JUN 2009
- Article first published online: 12 JUN 2009
- Accepted 28 May 2008. Published Online 12 June 2009.
- Host response;
- peroxisome proliferator activator receptor agonists;
Abstract Despite the best efforts of influenza scientists, companies and health officials to prepare for the next pandemic, most of the world’s people will not have access to affordable supplies of vaccines and antiviral agents. They will have to rely on 19th century public health ‘technologies’ to see them through. In the 21st century, science ought to be able to provide something better. Influenza scientists study the molecular characteristics of influenza viruses and their signaling effects in cell culture and animal models of infection. While these studies have been enormously informative, they have been unable to explain the system-wide effects of influenza on the host, the increased mortality of younger adults in the 1918 influenza pandemic and the much lower mortality rates in children who were more commonly infected with the 1918 virus. Experiments by non-influenza scientists have defined common cell signaling pathways for acute lung injury caused by different agents, including inactivated H5N1 influenza virus. These pathways include several molecular targets that are up-regulated in acute lung injury and down-regulated by anti-inflammatory and immunomodulatory agents, including statins, fibrates, and glitazones. These agents also help reverse the mitochondrial dysfunction that accompanies multi-organ failure, something often seen in fatal Influenza. Observational studies suggest that statins are beneficial in treating patients with pneumonia (there are no such studies for fibrates and glitazones). Other studies suggest that these agents might be able to ‘roll back’ the self-damaging host response of young adults to the less damaging response of children and thus save lives. Research is urgently needed to determine whether these and other agents that modify the host response might be useful in managing H5N1 influenza and the next pandemic.