Direct cytolysis by partially‐purified preparations of immune interferon

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Abstract
Mouse IFNγ preparations purified 30‐fold were found to have direct cytolytic activity against a number of tumor and normal cells. Cell killing was determined using a sensitive, rapid and accurate assay which employed very low numbers of cells and very small quantities of interferon. The cytolytic activity of IFNγ on 11 murine tumor cell lines was investigated. A 20‐fold difference was found between the most sensitive cell type, P‐388 lymphoma, versus the most resistant cell type, C127v leukemia. A number of normal mouse cells was also found to have low to intermediate sensitivity to the cytolytic action of IFNγ. Human IFNγ was also shown to have cytolytic activity which, like mouse IFNγ, was relatively species‐specific. Direct cytolysis was not found to be a characteristic of IFN‐α/β. Different mechanisms of action for the antiviral and cytolytic activities of IFNγ are indicated because the cytolytic titer of IFNγ did not parallel its antiviral titer on most cell types and increasing the cell number produced a decrease in the cytolytic titer and an increase in the antiviral titer. High concentrations of IFNγ (i.e., 2,900 units/ml) resulted in complete lysis of cells within 24 h, while lower concentrations (i.e., 700 units/ml) resulted in a reversible inhibition of cell growth during this time period. Evidence that the cytolytic substance in the IFNγ preparation was IFNγ include the following: (1) both antiviral and anticellular activities copurified through a 30‐fold purification; and both activities were (2) relatively speciesspecific; (3) sensitive to heat; (4) inactivated by low pH and (5) neutralized by antibodies to IFNγ. Therefore, we propose the possibility that direct cytolysis is yet another of IFNγ's distinctive antivities.