Tumor necrosis factor-alpha production of influenza A virus-infected macrophages and potentiating effect of lipopolysaccharides.
Influenza A virus infections are commonly associated with symptoms that suggest involvement of TNF-alpha. In this study, we exposed human monocytes, rat alveolar macrophages, and murine PU5-1.8 macrophages to influenza A virus, strain Puerto Rico 8. We observed a productive infection that was accompanied by TNF-alpha mRNA accumulation, TNF-alpha release and subsequent cell death. TNF-alpha production was dependent on exposure to live virus, in contrast to IFN release that was also induced by UV-inactivated virus. Most strikingly, low amounts of LPS (1 to 10 ng/ml) from Escherichia coli or Haemophilus influenzae were capable of strongly potentiating TNF-alpha production from virus-infected macrophages. The potentiating effect of LPS was neither due to increased survival of macrophages nor to altered virus multiplication, enhanced TNF-alpha gene expression, discharge of intracellular TNF-alpha stores, or shifts in the kinetics of TNF-alpha release. Thus, low amounts of LPS, which could easily be present in vivo, may serve as a potent trigger signal for TNF-alpha production from macrophages that have been primed by influenza A virus infection. These data suggest that the frequently observed serious complications of combined influenza A virus and bacterial infections may be partially due to a high TNF-alpha production.
Nain
M
M
Institute of Immunology, Philipps University, Marburg, West Germany.
Hinder
F
F
Gong
J H
JH
Schmidt
A
A
Bender
A
A
Sprenger
H
H
Gemsa
D
D
D015152:Blotting, Northern; D015870:Gene Expression; D006801:Humans; D066298:In Vitro Techniques; D009980:Influenza A virus / Q000378:metabolism; D007251:Influenza, Human / Q000276:immunology* / Q000382:microbiology / Q000503:physiopathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000382:microbiology* / Q000502:physiology; D008970:Molecular Weight; D012333:RNA, Messenger / Q000235:genetics; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis
D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D014764:Viral Proteins