Potent activation of mouse macrophages by recombinant interferon-γ

The ability of recombinant interferon-γ (IFN-γ) to activate mouse macrophages was investigated. The use of recombinant IFN-γ has the advantage of being devoid of contaminating lymphokines. Two preparations of IFN-γ were utilized, one which was not glycosylated and which was highly purified from Escherichia coli and another which was glycosylated and which was from transfected COS-7 monkey cells. Both preparations of recombinant IFN-γ activated murine macrophages to kill lymphoma and melanoma tumor targets, suggesting that glycosylation of the protein or the presence of other mammalian proteins is not essential for activation. Significant levels of cytolytic activity were induced from IFN-γ (1 to 10 units/ml). This activity was undiminished by treatment of the IFN-γ preparations with polymixin B at doses which neutralized endotoxin (50 μg/ml). Similarly, IFN-γ, at low concentrations, induced an inhibition of migration by macrophages. Based on antiviral activity, IFN-γ was shown to be 100 to 1000 times more potent than was IFN-β as a macrophage-activating agent. Taken together, these results demonstrate that murine IFN-γ is a macrophage-activating factor which is effective at physiological concentrations. Of particular interest is the observation that the nonglycosylated E. coli-derived IFN-γ is active and therefore may be of value for therapeutic studies, since it can be easily produced in large amounts.