Effect of granulocyte/macrophage colony-stimulating factor on human monocytes infected with influenza A virus. Enhancement of virus replication, cytokine release, and cytotoxicity.
The activating properties of granulocyte/macrophage (GM)-CSF were studied in vitro with human monocytes infected by influenza A virus. When monocytes were pretreated for 8 h with GM-CSF (100 U/ml) and then exposed to influenza A virus, de novo virus protein synthesis was enhanced, more virus particles were released, and cells were killed at a higher rate. In virus-infected monocytes, GM-CSF induced a more rapid IFN-alpha release and potentiated production of TNF-alpha, IL-1 beta, and IL-6. Although GM-CSF or influenza A virus were each capable of independently activating TNF-alpha, IL-1 beta, and IL-6 gene transcription, a combination of both induced a massive cytokine mRNA accumulation which was readily translated into bioactive protein. Thus, GM-CSF may display a Janus-like action by accelerating virus infection but also by priming monocytes for elevated cytokine production. Whether the facilitated influenza A virus replication caused by GM-CSF may be counterbalanced by an improved cytokine response remains to be studied under more complex in vivo conditions.
Bender
A
A
Institute of Immunology, Philipps University, Marburg, Germany.
Amann
U
U
Jäger
R
R
Nain
M
M
Gemsa
D
D
D001483:Base Sequence; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects* / Q000382:microbiology / Q000502:physiology; D014158:Transcription, Genetic / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
D016207:Cytokines; D016178:Granulocyte-Macrophage Colony-Stimulating Factor