Interferon, induced in lymphocytes either with viruses or cell lines, increases severalfold the natural cytotoxicity of human lymphocytes on target cell lines. Cell separation experiments support the hypothesis that interferon enhances the activity of natural killer cells rather than generating a new population of effector cells. In mixed culture of lymphocytes and cell lines in which endogenous interferon is produced, interferon mediates an enhancement of cytotoxicity that represents up to 70-90% of the observed cytotoxicity. The effect of interferon on target cells is antagonistic to the effect on the lymphocytes: the susceptibility to cell-mediated lysis of various cells upon pretreatment with interferon is decreased and in some cases almost completely suppressed. Interferon renders target cells resistant to natural killer cells acting by an intracellular mechanism which requires RNA and protein synthesis. While normal fibroblasts are protected, virus-infected cells and most tumor cells usually are not protected by interferon. Interferon by stimulating very efficient nonspecific cytotoxic cells and by protecting at the same time normal cells from lysis, might render the natural killer cell system an inducible selective defense mechanism against tumor and virus-infected cells.

https://rupress.org/jem/article-pdf/147/5/1314/1393333/1314.pdf

Anti-viral activity induced by culturing lymphocytes with tumor-derived or virus-transformed cells. Enhancement of human natural killer cell activity by interferon and antagonistic inhibition of susceptibility of target cells to lysis.

Plasminogen activation and regulation of pericellular proteolysis.

Purified mouse fibroblast interferon (IF) directly rendered resting macrophages tumoricidal. The physicochemical properties and species specificity of the stimulatory agent fall within the present definition of IF. Since a number of polyanions induce macrophage IF, the antitumor and antimicrobial activities may result from the ability of newly released IF to modify macrophage activity.

Interferon: an inducer of macrophage activation by polyanions.

Publisher Summary First described in 1957, interferons are induced animal proteins. A variety of stimulating substances can act as interferon inducers, and interferons inhibit a wide range of viruses by inducing an intracellular antiviral state; however, many interferons are species-specific in their antiviral activity. The suggestion that a few thousand molecules of interferon may induce an antiviral state indicates that they are among the most active biological substances. There are three general types of human interferon, designated alpha, beta, and gamma. When stimulated with virus, leukocytes in cultures produce predominantly the species called “alpha interferon.” There are at least 14 distinct genes for human alpha interferon. Most alpha interferons contain little or no carbohydrate. While human-beta interferon is usually species-specific and for the most part induces antiviral activity only in human cells, human-alpha interferons induce activity in human as well as some animal cell cultures. Gama interferon is antigenically distinct from them and is more labile to acid. Most alpha and beta interferons are quite stable at pH 2, while the antiviral activity of gamma interferon is significantly reduced.

Interferons with special emphasis on the immune system

A number of investigators have recently described specific cytotoxic effects of human lymphocytes against human target cells. For instance, in some studies cultured cell lines of tumor origin have been used as targets in attempts to demonstrate tumor-specific cell-mediated eytotoxicity (CMC) (Bubenik et al. 1971, Leventhal et al. 1972, Baldwin et al. 1973, Heilstrotn & Hellstrom 1974, O'Toole et al. 1974). Unfortunately these studies have been hampered by the fact that lymphocytes from normal donors were at least as reactive as those from cancer patients (Takasugi et al. 1973). Also, studies employing target cells infected with viruses (Steele et al. 1973, Labowskie et al. 1974, Rola-Plesczynski et al. 1975, 1976) have not produced convincing evidence for the existence of

Mechanisms of activation of human natural killer cells against tumor and virus-infected cells.

Previous studies have shown that interferon (IF) preparations enhance phagocytic activity in cultured mouse peritoneal macrophages. It is shown here that cell culture fluids containing large amounts of IF, which had been treated with acid and clarified of the inducer, Newcastle disease virus, enhanced phagocytic activity when injected into mice. Enhanced phagocytic activity also was observed after injection of Newcastle disease virus into mice, but the contribution of IF to this event was unclear. The kinetics of the phagocytic response to inducers in vivo were biphasic. Depression of phagocytosis occurred around 16 to 18 h after injection of Newcastle disease virus. The observed enhancement began about 12 h later and lasted for at least 60 h more. It was concluded that the complexity of the response of mice to an inducer makes analysis of the role of IF in the ensuing events difficult. However, because of documented phagocytosis-enhancing effects of IF in vitro, it is very likely that the in vivo effects observed here are to some degree mediated by IF. On this basis, the concept of the activity of IF as a lymphokine is potentially expanded.

https://iai.asm.org/content/iai/13/4/1250.full.pdf

K Y Huang

Papers

Interferon preparations enhance phagocytosis in vivo.