Human lymphokine preparations which generate tumoricidal properties of human monocytes in vitro may be distinct from gamma interferon.

The purpose of these studies was to determine whether stimulated human lymphocytes produce lymphokines distinct from IFN gamma, that can activate human blood monocytes to lyse tumor cells. We undertook this investigation because of the controversy concerning whether MAF and IFN gamma are the same molecule. Crude lymphokine preparations prepared from normal human mononuclear cells incubated with Con A and rich in MAF activity also contained 1000 U/ml IFN gamma as measured by the virus neutralization assay. However, the induction of tumoricidal activity in monocytes by the lymphokine preparation could be dissociated from the IFN gamma activity, based on the following data: (1) Heat treatment (100 degrees C for 2 min) removed the antiviral activity of the lymphokine yet did not diminish its MAF-like activity when measured in a 72 h cytotoxicity assay against 125I IUdR-labeled human A375 melanoma cells. (2) Likewise, treatment of this lymphokine preparation with a twofold excess of anti-IFN gamma antibody neutralized antiviral activity but once again had no effect on its ability to activate monocyte tumoricidal function. In contrast, both heat treatment and anti-IFN gamma antibody abolished monocyte activation by equivalent units of human recombinant IFN gamma. Taken together, these data suggest that there is a molecule(s) distinct from IFN gamma which can activate human monocytes for tumoricidal function. Furthermore, this dissociation of MAF and IFN gamma activity was dependent on the use of a long-term (72 h) assay, since activation of tumoricidal activity in an 18-24 h assay appeared to be attributable solely to IFN gamma.