Magnitude of influenza virus replication and cell damage is associated with interleukin-6 production in primary cultures of human tracheal epithelium

Primary cultures of human tracheal epithelium were infected with influenza viruses to examine the relationships between the magnitude of viral replication and infection-induced cell damage and cytokine production in airway epithelial cells. Infection with four strains of the type A influenza virus increased the detached cell number and lactate dehydrogenase (LDH) levels in the supernatants. The detached cell number and LDH levels were related to the viral titers and interleukin (IL)-6 levels and the nuclear factor kappa B (NF-κB) p65 activation. Treatment of the cells with an anti-IL-6 receptor antibody and an NF-κB inhibitor, caffeic acid phenethyl ester, reduced the detached cell number, viral titers and the LDH levels and improved cell viability after infection with the pandemic influenza virus [A/Sendai-H/N0633/2009 (H1N1) pdm09]. A caspase-3 inhibitor, benzyloxycarbonyl-DEVD-fluoromethyl ketone, reduced the detached cell number and viral titers. Influenza viral infection-induced cell damage may be partly related to the magnitude of viral replication, NF-κB-p65-mediated IL-6 production and caspase-3 activation.