M. Naqi Zafar  ( Zafar Research and Diagnostic Centre, 7/14, Riznpa Plaza, M.A. Jinnah Road, Karachi. )

Interferons are a group of inducible secretor.y glycoproteins of moleculor weight 15,000-20,030 daltons (Vilcek et al., 1977) synthesized by eukaryotic cells in response to viral infections and other stimuli e.g., mitogens and antigens. The ability to synthesize interferons is present in all vrertebrates and virtualiy all nucleated cells are capable of it; the only requisite being that the cells are metabolically active and that they are stimulated by an appropriate inducer, e.g., viruses (Vilcek et ., 1969), synthetic polynucleotide complexes (Field et ., 1967) and mitogens (Gresser, 1961). There are two major types of Interferons which are distinguished on the basis of resistance to low pH. Virally inducted, leucocyte, lymphoblastoid and fibroblast interferons are resistant to pH₂ and are termed as Type I. Interferons produced by mitogen or antiyen stimulated lymphoid cells are labile at pH₂ and designated as Type II and these are antigenically different from Type I (Youngner and Salvin, 1973).
Interferons have a variety of biological properties. They block the replication of a large variety of viruses in cells. These include single and double stranded RNA viruses, DNA containing viruses, lytic and transforming viruses (Friedman, 1977). The exact mechanism of this blocking effect is not certain however both virus-specific primary transcription and translation of virus RNA can be inhibited in Interferon treated cells (Joklik, 1977).
Interferons also affect the cell surface propertes. Their treatment enhances the absorption of alloantibody on the surface of leukaemic cells (Lindahi et al., 1973) and the expression of histocompatibility antigens on tumour cells, thymocytes and splenocytes (Lindahi et al. 1973; Yignaux and Gresser, 1977). Interestingly interferon induced changes have been shown to be diametrically opposed to the changes associated with viral induced transformation (Pfeffer et al, 1981).
Interferons have an inhibitory effect on cell growth. They inhibit the growth of both normal and transformed cells (Paucker et al., 1962). This effect also occurs invivo in regenerating liver cells (Frayssinet et al., 1973) and transplanted tumour cells (Gresser et al., 1977). Interferon treated cells do not appear to be blocked in any particular phase of their cell cycle but exhibit a proportional lengthening of each phase (Balkwill and Tayler, 1978).
The most important biological effect of luterferous is on the Immune system. In lymphoid cells the interferon induced phenotype includes a decrease in the rate of cell multiplication during the proliferative phase of the Immune response and an enhancement of antibody secretion and cytotoxicity during the non-proliferative phase of the response. These can result in either an inhibition or enhancement of an Immune response (Epstein, 1977). Interferons also inhibit delayed type hypersensitivity reactions to various antigens (DeMaeyer et al., 1975), they delay graft rejection (DeMaeyer, 1973) and graft-versus host reaction (Hirsch et al., 1973). They enhance the number of phagocytic macrophages and phagocytosis in vivo (Gresser et al., 1977) and enhance cell mediated cytotoxicity (Lindahl et al., 1972).
A natural cell mediated cytotoxicity has been described in man which is capable of causing in vitro lysis of virus infected and tumour cells. It is mediated by small lymphocytes which are without adherent properties, have Fc receptors but no surface markers for T and B cells and which differentiate from Bone marow precursor cells, the Natural Killer or NK cells. In vivo mouse Interferon is capable of inhibiting the growth of in vitro interferon resistant tumour cells (Gresser et al., 1972). Increased NK cell activity has been observed in animals injected with interferon inducers (Ochier et al., 1978; Herberman et al., 1977), Viruses and tumour cells (Trinchicri et al., 1977). It is now believed that the antitumour effect of Interferon is through the enhancement of NK cell activity (Senik et al., 1979). Hence enhancement of the NK cell activity has also been reported in cancer patients under treatment with leukocyte interferon (Einhorn et al., 1978; Hudolestone et aI., 1979).
The vaned projerties of Interferons, interaction with the Immune system and their involvement in recognition and defence against virus infected and cancer cells has resulted in enthusiastic research towards their role in cancer therapy which has started to give encouraging results.

1. Balkwill, F. and Tayler, W.D. (1978) Papadimitriou J: Inhibition by lymphoblastoid interferon of growth of cells derived from the human breast. Int. J. Cancer, 22:258.
2. DeMaeyer, E., DeMaeycr-Guignard, J. and Vandeputte, M. (1975) Inhibition by interferon of delayed type hypersensitivity in the mouse. Proc. Nati. Acad. Sci. USA., 72 :1753.
3. DeMaeyer, E., Mobraaten, L. and DeMaeyer-Guignard, J. (1973) Prolongation by interferon of the survival of skin grafts in the mouse. CR Acad. Sci. (Paris), D277:2l01-2103, 1973.
4. Epstein, L. The effects of interferons the immune on response in vitro and in vivo, in Stewart II WE (ed): Interferons and Their Actions: Cleveland, Ohio, CRC, 1977, pp. 92-132.
5. Einhorn, S., Blomgren, H. and Strander, H. (1978) Interferon and spontaneous cytotoxicity in man. I. Enhancement of spontaneous cytotoxicity of peripheral lymphocytes by human leukocyte interferon. Int. J. Cancer, 42 :405.
6. Field, A.K., Tytell, A.A., Lampson, G.P. and Hilleman, M.R. (1967) Inducers of interferon and host resistance II. Multistranded synthetic polynucleotide complexes. Proc. Natl. Acad. Sci. USA., 58:1004.
7. Iriedman, R.M. (1977) Antiviral activity of interferons. Bacteriol. Rev., 41:543.
8. Frayssinet, C., Gressor, I., Tovey, M. and Lindahi, P. (1973) Inhibitory effect of potent interferon preparations on the regeneration of mouse liver after partial hepatectomy. Nature, 245:146.
9. Gresser, I. (1961) Production of interferon by suspensions of human leukocytes. Proc. Soc. Exp. Biol. Med., 108:799.
10. Gresser, I., Maury, C. and Brouty-Boye, D. Antitumor effects of interferon, in Cancer; a comprehensive treaties, Edited by F. Becker. Vol. 5, New York, Plenum, 1977, pp. 521-571.
11. Gresser, I., Maury, C. and Brouty-Boye, D. (1972) Mechanism of the antitumor effect of interferon in mice. Nature, 239 :167.
12. Hirsch, M.S., Ellis, D.A., Proffit, M.R. and Black, P.H. (1973) Effects of interferon on leukemia virus activation in graft versus host disease. Nature, (New Biol) 244:102.
13. Herberman, R.B., Nunn, M.E., Holden, H.T., Staal, S. and Djeu, J.Y. (1977) Augmentation of natural cytotoxic reactivity of mouse lymphoid cells against syngeneic and allogenic target cells. Int. J. Cancer, 19:555.
14. Fluddlestone, J.R., Merigan, T.C. Jr. and Oldstone, M.B.A. (1979) Induction and kinetics of natural killer cells in human following interferon therapy. Nature, 282:417.
15. Joklik, W.K. (1977) The mechanism of interferon action. Ann. N.Y. Acad. Sci., 284:711.
16. Lindahi, P., Leary, P. and Gresser, I. (1973) Enhancement by interferon of the expression of surface antigens on murine leukemia L1210 cells. Proc. Natl. Acad. Sci. USA., 70:2785.
17. Lindahi, P., Leary, P. and Gresser, I. (1972) Enhancement by interferon of the specific cytotoxicity of sensitized lymphocytes. Proc. NatI. Acad. Sci. USA., 69:721.
18. Ochier, J.R., Lindsag, L.R., Nunn, M.E., Holden, H.T. and Herber-man, R.B. (1978) Natural cell-mediated cytotoxicity in ats. II. In vivo augmentation of NK-cell activity. Int. J. Cancer, 21:210.
19. Pfeffer, L.M., Wang, E., Landsberger, F.K. and Tamm, I. Plasma memberane and cytoskeleton of interferon-treated human cells, in Krim M, Edy VG, Oetigen H. Stewart H WE (ed): Report of the 2nd International Workshop on Interferons. New York, Rockefeller University Press, 1981.
20. Paucker, K., Cantell, K. and Henle, W. (1962) Quantitative studies on viral interference in suspended L cells. III. Effect of interfering viruses and interferon on the growth rate of cells. Virology, 17:324.
21. Senik, A., Gresser, I., Maury, C., Gidlund, M., Orn, A. and Wigzell, H. (1979) Enhancement by interferon of natural killer cell activity in mice. Cell. Immunol., 44:186.
22. Trinchicri, G., Santoli, D. and Knowles, B.B. (1977) ‘rumour cell lines induce interferon in human lymphocytes. Nature, 270 :611.
23. Vilcek, j., Rossman, T.G. and Varacalli, F. (1969) Differential effects of actinomycin on the release of interferon induced by double-stranded RNA. Nature, 222:682.
24. Vilcek, J., Havell, E.A. and Yarnazaki, S. (1977) Antigenic, physicochemical and biologic characterization of human interferons. Ann. N.Y. Acad. Sci., 284:703.
25. Vignaux, F. and Gressër, I. (1977) Differential effects, of interferon on the expression of H-2K, H-2D and ia antigens on mouse lymphocytes. J. Immunol., 118:721.
26. Youngner, J.S. and Salvin, S.B. (1973) Production and properties of migration inhibitory factor and interferon in the circulation of mice with delayed hypersensitivity. J. Immunol., III: 1914.