Interferon as a macrophage activating factor. I. Enhancement of cytotoxicity by fresh and matured human monocytes in the absence of other soluble signals
The cytolytic activity ofhuman peripheral blood monocytes in vitro against K-562 human
leukaemic target cells was stimulated by human fibroblast (fi-) and leucocyte (a-)
interferon (IFN). Stimulation was by up to several times the corresponding control
activity, and was observed with freshly isolated monocytes, and with monocytes cultured
for various periods up to 10 days. The cytolytic activity of untreated monocytes was
detectable at very low effector: target ratios ( < 5: 1), and fell between days 1 and 4 in
culture, normally rising again towards the initial activity at day 8; this pattern was also
observed when IFN was present continuously, although the activities were then always
higher than in the corresponding control cells. Cytolysis showed a lag of about 6 hr, in
contrast to that by natural killer (NK) cells, and was routinely measured over 24 hr. The
course of stimulation by IFN and its dose-response were studied. Stimulation required
the presence of IFN for at least 24 hr, and was maximal with between 1,000 and 10,000
units of IFN/ml. When IFN containing media were removed and replaced with control
media, the monocyte activity remained stimulated for at least 4 days. Stimulation by
fl-IFN was blocked by a specific antibody to fl-IFN, under conditions in which assayable
IFN activity was also neutralized. Several control experiments indicated that the action of
IFN was on the monocytes and not on the target cells. The morphological maturation of
monocytes was retarded by IFN, even in cultures containing up to 50% serum. The
effectiveness of fibroblast IFN indicated that stimulation could not be attributed to the
lymphokines which might contaminate a-IFN. The action of IFN did not require
simultaneous or antecedent in vitro stimulation by endotoxin. This was indicated both by
serum free experiments, and also by others in which polymixin B was used to complex with
and render unavailable any endotoxin present. Endotoxin showed an independent
stimulatory effect, which could be prevented by polymixin
