Influence of interferon on human monocyte to macrophage development.

The effect of interferon-alpha (Wellferon) on human monocyte to macrophage maturation in vitro has been investigated. Cell volume and three markers, acid phosphatase, leucine aminopeptidase, and phagocytosis, which increase with maturation, have been studied employing recently developed flow cytofluorometric techniques. The increase in cell volume and in the expression of all three markers was inhibited in a dose-dependent manner in monocyte cultures given 50-300 U/ml of interferon within 2 hr of culture initiation. An initial dose of 300 U/ml of interferon, removed from the cultures after 24 hr, was as effective in inhibiting the development of each of the markers as three 100 U pulses on three consecutive days, and as effective as 300 U interferon left in throughout the culture period. Histogram analysis of marker expression indicated that all monocytes, and not a subpopulation, were affected by the interferon. Cytotoxic activity of freshly isolated monocytes rapidly decayed when the cells were cultured under standard maturation conditions. The addition of interferon to the cultures prevented the loss of this activity while also preventing the development of more mature cells. It appears that maintenance of the cytotoxic state is one influence of interferons; however, it may be that these cells have also been directed toward alternate pathways of macrophage differentiation.