Faculty Bibliography

Inhibitory effects of two human interferon preparations, leukocyte interferon (Le-IF) and fibroblast interferon (F-IF), on granulocytic progenitor cells (CFU-C) from hematologically normal cancer patients and from patients with chronic myelogenous leukemia were evaluated. There was a wide variation in sensitivity of CFU-C to both Le-IF and F-IF. F-IF was mor inhibitory against CFU-C than le-If. Normal CFU-C and chronic myelogenous leukemia CFU-C were equally inhibited by both interferons. Effects of both interferons were neutralized by corresponding specific antisera but not by the other antisera. These observations confirmed that differences in immunogenicity of the interferons may attend their different origins

Human F and Le interferon can be clearly distinguished on the basis of different antigenic properties and host range. After inoculation with Newcastle disease virus (NDV), GM-258 fibroblasts produced Le as well as F interferon; in contrast, only F interferon was detectable after stimulation with poly(I) . poly(C). Polyadenylylated mRNA isolated from fibroblasts induced with poly(I) . poly(C) or NDV was injected into Xenopus laevis oocytes and the interferon activities thus produced were analyzed. Only F interferon production was demonstrable in oocytes injected with mRNA from cells induced with poly(I) . poly(C), whereas both F and Le interferons were made in oocytes injected with mRNA from NDV-induced cultures. The time course of accumulation of F and Le interferon mRNAs in NDV-induced cells corresponded to the kinetics of F and Le interferon synthesis in intact cells. The ratio of F and Le interferons made in oocytes was similar to that observed in intact GM-258 cells. F and Le interferon mRNA activities isolated from GM-258 cells could not be separated by sucrose density gradient centrifugation. However, the profile of F mRNA activity was more heterogeneous and its peak sedimented somewhat more slowly than that of Le interferon mRNA. These results suggest that the varying ratios of F and Le interferon synthesis in different cells after different modes of stimulation are determined at the level of mRNA. The induction mechanisms of F and Le interferon mRNA synthesis appear to be closely related but not identical

We previously reported that polyinosinic-polycytidylic acid, a potent interferon inducer, inhibits the growth of B16 malignant melanoma in the C57BL/6 mouse. Two experiments were done to evaluate the effectiveness of interferon in tumor inhibition in vivo. In the first, mice were implanted with melanoma and divided into four groups, according to treatment: interferon preparation; interferon control preparation ('breakthrough fraction'); phosphate-buffered saline control; and murine serum albumin control. Daily, each mouse was given i.p. injections of 200,000 NIH reference units (hereafter called units) of interferon or of one of the control substances. The second experiment was similar to the first, except that bovine serum albumin was an additional control. In both experiments, the average tumor volume in interferon-treated mice was statistically significantly smaller than that of each control group. Mouse interferon preparations also inhibited the multiplication of B16 malignant melanoma cells in culture. This inhibition was statistically significant from interferon levels as low as 5 to as high as 5000 units/ml. The degree of inhibition markedly increased from 5 up to 500 units, the inhibition reaching its maximum at this concentration. The inhibitory effect of interferon was abrogated by anti-murine interferon serum produced in a rabbit. These findings suggest that the in vivo inhibition of the growth of B16 melanoma demonstrated with polyinosinicpolycytidylic acid and with exogenous interferon probably results, at least in part, from a direct effect of interferon on the tumor cells themselves

When rabbits were given intramuscular injections of the same quantities of human leukocyte or fibroblast interferons, the former produced moderately higher levels of circulating interferon. Fibroblast interferon was not cleared faster from circulation, nor was direct inactivation by rabbit blood responsible for this difference

Inducers of the Epstein-Barr virus (EBV) cycle, 5-iodo-2-deoxyuridine (IdUrd), phorbol myristate acetate (TPA) and sodium butyrate were tested for their ability to induce EBV-determined antigens, early antigen (EA) and virus capsid antigen (VCA), and to stimulate interferon (IF) production in a variety of EBV-carrying lymphoid cell lines. IdUrd and TPA induced IF production to various extents in the different lines, whereas sodium butyrate did not. There was no relationship between induction of the EBV cycle and production of IF; the two appear to be independent characteristics. Superinfection with the transforming B95-8 virus substrain of EBV induced IF production, whereas superinfection with the abortively cytopathic, non-transforming P3HR-1 substrain had little or no IF-inducing effect, in spite of its highly potent effect on virus antigen (particularly EA) synthesis. Analysis with specific antisera against IF showed that IF preparations produced by three different lymphoid cell lines in response to IdUrd treatment were composed of a mixture of the Le and F antigenic types, with the latter forming a minor species. In contrast, no detectable F interferon was present in spontaneously produced IF preparations from Namalwa cells, or after induction with B95-8 virus