Direct cytolysis by partially‐purified preparations of immune interferon

Abstract

Mouse IFN gamma 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 IFN gamma 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 IFN gamma. Human IFN gamma was also shown to have cytolytic activity which, like mouse IFN gamma, was relatively species-specific. Direct cytolysis was not found to be a characteristic of IFN-alpha/beta. Different mechanisms of action for the antiviral and cytolytic activities of IFN gamma are indicated because the cytolytic titer of IFN gamma 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 anti-viral titer. High concentrations of IFN gamma (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 IFN gamma preparation was IFN gamma include the following: (1) both antiviral and anticellular activities copurified through a 30-fold purification; and both activities were (2) relatively species-specific; (3) sensitive to heat; (4) inactivated by low pH and (5) neutralized by antibodies to IFN gamma. Therefore, we propose the possibility that direct cytolysis is yet another of IFN gamma's distinctive antivities.

Mouse Macrophages Carrying Both Subunits of the Human Interferon-γ (IFN-γ) Receptor Respond to Human IFN-γ but Do Not Acquire Full Protection against Viral Cytopathic Effect

“…1 is a pleiotrophic cytokine that influences a variety of biological responses including induction of antiviral states, antiproliferative activity, and immunomodulation within responsive cell types (1)(2)(3)(4)(5). An early event in each of these responses is the binding of hu-IFN-␥ to the hu-IFN-␥R1 chain (p90 chain; ligand binding chain) which is encoded by a gene localized on human Chromosome 6 (6).…”

Identification of a yeast artificial chromosome clone encoding an accessory factor for the human interferon gamma receptor: evidence for multiple accessory factors.

“…Human interferon y (Hu-IFN-y) is a protein that induces a variety of biological responses such as antiviral, antiproliferative, and immunomodulatory activities in sensitive ceils (1)(2)(3)(4)(5). Immunoregulatory functions induced by Hu-IFN-y, such as induction ofclass I and class II human HLA antigens, activation of macrophages, regulation of immunoglobulin class switching, and up-regulation of Fc receptor expression are involved in modulating a variety of other host defense mechanisms (5)(6)(7)(8)(9)(10).…”

Successful treatment of colon cancer in rats with recombinant interferon-gamma

“…However it should be noted that these experiments were performed with IFNs that were only partially purified and possibly contained contaminating cytokines that could have contributed to the biological effects. IFN-y has been reported to exert a direct cytotoxic effect on certain tumour cell lines (Tyring et al, 1982). In addition, a number of immunological functions influenced by IFN-y may synergize with this direct cytotoxic action.…”