Natural interferons

T. Eto and H. Takahashi, Enhanced inhibition of hepatitis B virus production by asialoglycoprotein receptor-directed interferon, Nature Med. 5 577-581 (1999). 

A7. Aggarwal, B. B., Eessalu, T. E., and Hass, P. E. Characterization of receptors for human tumor necrosis factor and their regulation by gamma-interferon. Nature (London) 318, 665-667 (1985). 

Pober, J. S., Collins, T., Gimbrone, M. A., Cotran, R. S., Gitlin, J. D., Fiers, W., Clayberger, C., Krensky, A. M., Burakoff, S. J., and Reiss, C. S. Lymphocytes recognize human vascular endothelial and dermal fibroblast la antigens induced by recombinant immune interferon. Nature (London) 305, 726-729 (1983). 

In the early stage of viral infection there is an intensive race between the virus and the host s defense systems, which are mediated through (1) nonspecific or innate immune defenses by interferon, natural killer (NK) cells, complement cascade, apoptosis, and macrophages (2) specific or adaptive immune defenses by cytotoxic T lymphocytes (CTL), helper T lymphocytes, and anti-viral antibodies (Ploegh 1998). The conclusion of this race will depend on how rapidly the virus can infect and/or replicate before it is cleared by an active immune system. 

DiaZepin Nucleosides. Four naturally occurring dia2epin nucleosides, coformycin (58), 2 -deoxycoformycin (59), adechlorin or 2 -chloro-2 -deoxycoformycin (60), and adecypenol (61), have been isolated (1—4,174,175). The biosynthesis of (59) and (60) have been reported to proceed from adenosine and C-1 of D-ribose (30,176,177). They are strong inhibitors of adenosine deaminase and AMP deaminase (178). Compound (58) protects adenosine and formycin (12) from deamination by adenosine deaminase. Advanced hairy cell leukemia has shown rapid response to (59) with or without a-or P-interferon treatment (179—187). In addition, (59) affects interleukin-2 production, receptor expression on human T-ceUs, DNA repair synthesis, immunosuppression, natural killer cell activity, and cytokine production (188—194). 

Viral infections continue to be significant causes of morbidity and mortality and at the same time continue to be resistant to treatment by small molecules. Avridine (6) is an antiviral compound which has shown some activity in a variety of animal tests apparently based upon its ability to stimulate a number of cells to produce the high molecular weight endogenous antiviral substance interferon. Thus, the compound is believed to operate indirectly by stimulating the body s own natural defenses against viral penetration into host cells. Avridine is synthesized by... 

Interferon (IFN) differs from bona fide antiviral diugs since it is a natural defense protein of the host organism and does not directly interfere with the viral replication steps. Interferons are small glycoproteins inducing immune modulatory and antiviral activities. They are secreted by lymphocytes, leukocytes and fibroblasts in response to foreign nucleic acids (dsRNA). 

Immune Defense. Figure 2 Cytokines involved in the development of adaptive immune responses in secondary lympoid tissues such as the lymph nodes or spleen. Abbreviations B B-lymphocyte, IFN interferon, Ig immunoglobulin, IL interleukin, NK natural killer cell, TE T-effector (cytotoxic) lymphocyte, TH T-helper lymphocyte... 

Honda K, Yanai H, Negishi H, Asagiri M, Sato M, Mizutani T, Shimada N, Ohba Y, Takaoka A, Yoshida N, Taniguchi T (2005) IRF-7 is the master reguiator of type-I interferon-dependent immune responses. Nature 434 772-777... 

Nagata S, Taira H, Hall A, Johnsrud L, Streuli M, Ecsodi J, Boll W, CanteU K, Weissmann C (1980) Synthesis in E. coli of a polypeptide with human leukocyte interferon activity. Nature 284 316-320... 

Osborn BL, Olsen HS, NardeUi B, Murray JH, Zhou JX, Garcia A, Moody G, Zaritskaya LS, Sung C (2002) Pharmacokinetic and pharmacodynamic studies of a human serum albumin-interferon-alpha fusion protein in cynomolgus monkeys. J Pharmacol Exp Ther 303 540-548 Ozes ON, Reiter Z, Klein S, Blatt LM, Taylor MW (1992) A comparison of interferon-Conl with natural recombinant interferons-alpha antiviral, antiproliferative, and natural kiUer-inducing activities. J Interferon Res 12 55-59... 

Shiratori Y, Nakata R, Shimizu N, Katada H, Hisamitsu S, Yasuda E, Matsumura M, Narita T, Kawada K, Omata M (2000) High viral eradication with a daily 12-week natural interferon-beta treatment regimen in chronic hepatitis C patients with low viral load. Dig Dis Sci 45 2414-2421 Sidwell RW, Huffman JH, Khare GP, Allen LB, Witkowski JT, Robins RK (1972) Broad-spectrum antiviral activity of Virazole l-beta-D-ribofuranosyl-l,2,4-triazole-3-carboxamide. Science 177 705-706... 

Kadowaki N. Antonenko S, Lau JY, Liu YJ Natural 45 interferon a/p-producing cells link irmate and adaptive immunity. J Exp Med 2000 192 219-226. 

Innate immune response to viral infections is predominately through interferon-alpha, -beta (IFN-a and -P) induction and activation of natural killer (NK) cells. Although viral replication can induce IFN-a and -P expression, macrophages are capable of producing and secreting cytokines which also induce the production of these type I interferons (Falk 2001). Bound IFNa and p to its receptors on NK cells increases its ability to lyse virally-infected cells. 

Proteins produced by virally infected cells have been shown to interfere with viral replication. They also activate leucocytes that can recognize these infected cells and subsequently kill them. These leucocytes are known as natural killer (NK) cells and the proteins are termed interferons (see also Chapters 3, 5 and 24). 

Goeddel D.V., Yelverton E., Ullrich A, Heyneker H.L., Miozzari G., Holmes W., Seeburg P.J., Dull T., May L, Stebbing N., Crea R., Maeda S., McCandliss R, Sloma A, Tabor J.M., Gross M., Eamilletti P.C. Pestka S. (1980) Human leukocyte interferon produced by E. coli is biologically active. Nature, 287,411-416. 

The sterols and sterolins in rice bran are potent immunomodulators. The best response was obtained with a 100 1 sterol/sterolin mixture that demonstrated T-cell proliferation from 20% to 920% and active cell antigens after four weeks in human subjects (Bouic et al, 1996). Another in vitro experimental study with sterol/sterolins, demonstrated a significant increase in cytokinines, interleukin-2 and y-interferon between 17% and 41 % in addition to an increase in natural killer cell activity. These experiments (Bouic et al, 1996) prove that sterol/sterolins are potent immunomodulators with important implications for the treatment of immune dysfunction. Rice bran products are excellent dietary supplements for the improvement of immune function. It is probable that the effects of rice bran on diabetes, CVD and cancer all result from improved immune function. 

Kim JH, Kim HY, Kim S, Chung JH, Park WS, Chung DH. Natural killer T (NKT) cells attenuate bleomycin-induced pulmonary fibrosis by producing interferon-gamma. Am J Pathol 2005 167(5) 1231-1241. 

Biotechnology era beginning First recombinant DNA products Human insulin Human growth hormone Interferons, etc. Monoclonal antibodies Nucleotide blockage Growth in use of natural products and neutraceuticals... 

SMA-NCS can also be used to activate macrophages, natural cells, and T cells and to induce interferon-gamma production [265]. 

P10. Philip, R., and Epstein, L. B., Tumour necrosis factor as immunomodulator and mediator of monocyte cytotoxicity induced by itself, gamma-interferon and interleukin-1. Nature 323, 86-89(1986). 

Siegal, F.P., Kadowaki, N., Shodell, M., Fitzgerald-Bocarsly, P.A., Shah, K., Ho, S., Antonenko, S. and Liu, YJ. (1999) The nature of principal type 1 interferon-producing cells in human blood. Science 284,1835-1837. 

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