PRODUCTION OF LIPOPOLYSACCHARIDE-INDUCED TUMOR-NECROSIS-FACTOR DURINGINFLUENZA-VIRUS INFECTION IN MICE COINCIDES WITH VIRAL REPLICATION AND RESPIRATORY OXIDATIVE BURST

INCREASED morbidity and mortality occur regularly during influenza epi demics. The exact mechanisms involved are not well defined but bacteri al superinfection of influenza virus infected patients is considered t o play an important role. In the present study, the effect of influenz a virus infection on in vivo production of tumour necrosis factor (TNF ) in response to bacterial stimuli was investigated Release of TNF in mice infected by an aerosol of influenza virus was significant after a dministration of bacterial lipopolysaccharide (LPS) at 72h, whereas ad ministration of homologous influenza virus produced only modest amount s of TNF at 96h. Significant production of TNF was observed 48h after intravenous administration of infectious influenza in response to LPS but not with the homologous virus. TNF induced after influenza virus i nfection could be blocked by a specific murine anti-TNF monoclonal ant ibody. Higher TNF production following aerosol influenza infection cor related with peak titres of influenza virus in the lungs of infected m ice and with enhanced generation of luminol-dependent chemiluminscence .