The number of seasonal influenza deaths is highest in the very young or very old. However, certain influenza epidemics and pandemics, such as the 1918 ‘Spanish flu’, disproportionately kill otherwise healthy individuals. It is thought that highly pathogenic (HP) influenza strains stimulate a stronger immune response than seasonal strains, causing severe vascular leakage and lung edema, and eventual death. Aldridge et al. studied mouse immune cell responses following exposure to mouse-adapted influenza viruses that mimic either a seasonal flu or a HP flu strain. Compared with a sub-lethal strain, the HP strain recruited large numbers of TNF-α/inducible nitric oxide synthase-producing dendritic cells (tipDCs) to the lung. Whereas complete elimination of tipDCs results in lethality, limiting the tipDC response with pioglitazone, a peroxisome proliferator-activated receptor (PPAR)-γ agonist used to treat type II diabetes, improved viral tolerance in mice. Pioglitazone administration decreased mortality and improved recovery from HP strains of influenza, suggesting potential for its use as a therapeutic defense against pandemic forms of influenza.
Aldridge J.R. Jr, Moseley C.E., Boltz D.A., Negovetich N.J., Reynolds C., Franks J., Brown S.A., Doherty P.C., Webster R.G., Thomas P.G.. (2009). TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci USA 106, 5306– 5311.
