The use of
vaccines is the most effective and reliable method for the prevention of
viral infections. However, research on evaluation of effective therapeutic agents for use in treatment after
infection is necessary.
Zanamivir was administered through inhalation for treatment of pandemic
influenza A/H1N1 in 2009. However, the emergence of
drug-resistant strains can occur rapidly.
Alloferon, an immunomodulatory
drug developed as an NK cell activator, exerts
antiviral effects against various viruses, particularly influenza viruses. Therefore,
alloferon and
zanamivir were administered in combination in an effort to improve the
antiviral effect of
zanamivir by reducing H1N1 resistance. First, we confirmed that administration of combined treatment would result in effective inhibition of viral proliferation in MDCK and A549 cells infected with H1N1. Production of
IL-6 and MIP-1α in these cells and the activity of
p38 MAPK and c-Jun that are increased by H1N1 were inhibited by combined treatment. Mice were then infected intranasally with H1N1, and examination of the
antiviral efficacy of the
alloferon/
zanamivir combination was performed. The results showed that combined treatment after
infection with H1N1 prevented
weight loss, increased the survival rate, and improved lung
fibrosis. Combined treatment also resulted in reduced infiltration of neutrophils and macrophages into the lungs. Combined treatment effectively inhibited the activity of
p38 MAPK and c-Jun in lung tissue, which was increased by
infection with H1N1. Therefore, the combination of
alloferon/
zanamivir effectively prevents the development of H1N1-mediated
inflammation in the lungs by inhibiting the production of inflammatory mediators and migration of inflammatory cells into lung tissue.