Nasal cytokine and chemokine responses in experimental influenza A virus infection: Results of a placebo-controlled trial of intravenous zanamivir treatment

The local immune response to influenza virus infection was characterized by determining cytokine and chemokine levels in serial nasal lavage fluid sam ples from 15 volunteers experimentally infected with influenza A/Texas136/9 1 (H1N1), The study was Dart of a randomized double-blind placebo-controlle d trial to determine the prophylactic effect of intravenous zanamivir (600 mg 2 x /day for 5 days), a highly selective inhibitor of influenza A and B virus neuraminidases, on the clinical symptoms of influenza infection. Nasa l lavage fluid levels of interleukin (IL)-6, tumor necrosis factor-alpha, i nterferon-gamma, IL-10, monocyte chemotactic protein-1, and macrophage infl ammatory protein-1 alpha and -1 beta increased in response to influenza vir us infection and correlated statistically with the magnitude and time cours e of the symptoms. Treatment with zanamivir prevented the infection and abr ogated the local cytokine and chemokine responses. These results reveal a c omplex interplay of cytokines and chemokines in the development of symptoms and resolution of influenza.