ISG15 and infection: However, upon infection, levels of released IFN-γ and IL-1β cytokines were diminished in ISG15−/− mice but not in control C57BL/6 mice or in UbE1L−/− mice, which are devoid of intracellular conjugation of ISG15 through ISG15 E1 enzyme deficiency (12, 20) (Fig. 1C).