Abstract
Influenza A virus (IAV) is one of the most common infectious pathogens in humans, and it can cause significant morbidity and mortality in infants and the elderly with underlying diseases. The knowledge gained within the last decade in the IAV (H1N1) pandemic of 2009 and the highly pathogenic avian influenza outbreak improved our understanding not only of the viral pathogenicity but also the host cellular factors involved in the pathogenicity of multiple organ failure, such as cellular viral hemagglutinin processing proteases for viral multiplication, cytokine storm, metabolic disorders, and energy crises. Recently, a new concept of the pathogenicity of multiple organ failure has been proposed, the “influenza virus-cytokine-trypsin” cycle, involving up-regulation of ectopic pancreatic trypsin through pro-inflammatory cytokines, and potentiation of viral multiplication in various organs. We also found that the influenza virus-cytokine-trypsin cycle interrelated with the “metabolic disorders-cytokine” cycle, which is one of the principal mechanisms of the pathogenicity of multiple organ failure. These cycles provide new concepts for treatment of metabolic disorders and multiple organ failure, apart from antiviral neuraminidase inhibitors. Furthermore, we found that clarithromycin, an immunomodulating macrolide antibiotic, enhances mucosal and systemic immune responses and reduces the reinfection rate in pediatric patients with influenza treated with antiviral neuraminidase inhibitors. This review discusses IAV pathogenicity and available therapeutic options including immunomodulatory clarithromycin for prevention of IAV reinfection.
