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 stud ied 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 expo sed to influenza A virus, de novo virus protein synthesis was enhanced , more virus particles were released, and cells were killed at a highe r rate. In virus-infected monocytes, GM-CSF induced a more rapid IFN-a lpha release and potentiated production of TNF-alpha, IL-1beta, and IL -6. Although GM-CSF or influenza A virus were each capable of independ ently activating TNF-alpha, IL-1beta, and IL-6 gene transcription, a c ombination of both induced a massive cytokine mRNA accumulation which was readily translated into bioactive protein. Thus, GM-CSF may displa y a janus-like action by accelerating virus infection but also by prim ing monocytes for elevated cytokine production. Whether the facilitate d influenza A virus replication caused by GM-CSF may be counterbalance d by an improved cytokine response remains to be studied under more co mplex in vivo conditions.