| Interferon gamma (IFN-gamma) produced early in the course of mitogen stimulation of lymphocytes had an ability to protect cells against virus infection equivalent to that of IFN-alpha/beta. IFN-gamma produced later in the course of mitogen stimulation showed a decreased ability, suggesting the presence of an inhibitor.; An inhibitor of interferon action was found which migrated through a molecular sieving column with the leading edge (high molecular weight side) but not the trailing edge (low molecular weight side) of the IFN-gamma peaks.; Various chromatographic methods and physicochemical treatments of the IFN-gamma/inhibitor preparation failed to separate the inhibitor and IFN-gamma activities. In addition, a preparation of recombinant mouse IFN-gamma produced in E. coli, showed inhibitor activity. Further, inhibitor activity could be removed from the IFN-gamma/inhibitor preparation by treating these preparations with a combination of the reducing agent dithiothreitol (DDT), and the denaturant urea.; These data suggested that the inhibitor was associated with IFN-gamma and was most likely an altered IFN-gamma molecule. The IFN-gamma molecule thus appears to undergo a reversible alteration which gives rise to the inhibitor. Treatment of the inhibitor with DDT and urea then converts it back to IFN-gamma.; Inhibitor appears to generated whenever IFN-gamma levels are high. Further, inhibitor activity is independent of IFN-gamma concentration and is most dramatic and most complete when it is present at a high level. Thus, the inhibitor may represent a regulatory means for the local control of IFN-gamma induced activities when the levels of IFN-gamma reach too high a concentration. |
