Abstract
ST 789 is a synthetic compound which belongs to a new family of hypoxanthine derivatives exhibiting an aminoacidic function at the N-9 position of the purine ring (Cornaglia-Ferraris et al., 1984). Available literature indicates that hypoxanthine derivatives exhibit well established immunomodulant properties (Cornaglia-Ferraris et al., 1984). Furthermore, the addition of arginine to these molecules proved able to strongly enhance their immunomodulant activity. We review here the immunomodulant properties of both arginine and arginine-containing compounds, and mostly of ST 789. Furthermore, we report the results of preliminary experiments performed in our laboratory to better understand the mechanisms accounting for the immunomodulant activity of ST 789.
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References
Albina, J. E., Caldwell, M. D., Henry, W. L. Jr, Mills, C.D.,1989, Regulation of macrophage functions by L-Arginine, J Exp Med 169: 1021–1029.
Baldinelli, L., Biselli, R., Fattorossi, A., 1991 (in press),Influence of ST 789 on murine thymocytes: a flow cytometry study of thymocyte subset distribution and of intracellular free Ca++ increase upon activation, Thymus.
Barbui, A., Wasserkrug, H. L., Seifter, E., Rettura, G., Levenson, S. M., Efron, G., 1980, Immunostimulatory effects of arginine in normal and injured rats, J Surg Res 29: 228–235.
Barbul, A., Rettura, G., Levenson, S. M., Seifter, E., Wound healing and thymotrophic effects of arginine: a pituitary mechanism of action, 1983, Am J Clin Nutr 37: 786–794.
Comaglia-Ferraris, P., Coffey, R. G., Hadden, J.W., Substituted purines as immunomodulators: speculative considerations, 1984, J Immunol Immunopharmacol 2: 134–141.
Cornaglia-Ferraris,P., 1985, Immunomodulatory properties of a N-9 arginyl hypo-xantine derivative (PCF-39), Int J Immunopharmacol 7: 338–346.
Daly, J. M., Reynolds, J. V., Thon, A. K., Kinsley, L., Dietrich-Gallagher, M., Shou, J., Ruggieri, B., 1988, Immune and metabolic effects of arginine in the surgical patient, Am Surgery 208: 512–533.
Daly, J. M., Reynolds, J., Sigal, R. K., Shou, J., Liberman, M. D., 1990, Effect of dietary protein and amino-acids on immune function, Crit Care Med 18: 86–93. y
Fabris, N., Moccheggiani, E., Muzzioli, M., Provinciali, M.,19881, Neuroedocrine-thymus interactions: perspectives for intervention in aging, Ann NY Acad Sci 521: 72–87.
Fabris, N., Moccheggiani, E., 1991 (in press), Arginine-containing compounds and thymic endocrine activity, Thymus.
Famularo, G., Giacomelli, R., Valdamini, D., De Simone, C., Tonietti, G., 1991 (in press), Modulation by ST 789 of in vitro lymphocyte activation and cytokine production, Thymus.
Foresta, P., Riccardi, C., 1991 (in press), Immunorestorative properties of ST 789 on experimentally immunosuppressed and infected mice, 1991 (in press), Thymus.
Forni, G., Giovarelli, M., Santoni, A., 1985, Lymphokine-activated tumor inhibition in vivo. The local administration of interleukin 2 triggers nonreactive lymphocytes from tumor bearing mice to inhibit tumor growth, J Immunol, 134: 1305–1311.
Giovarelli, M., Cofano, F., Vecchi, A., Forni, M., Landolfo, S., Forni, G., 1986, Interferon-activated tumor inhibition in vivo: small amounts of interferon-gamma inhibit tumor growth by eliciting host systemic immunoreactivity, Int J Cancer 37: 141–148.
Giovarelli, M., Arione, R., Jemma, C., Musso, T., Benetton, G., Forni, G., Comaglia-Ferraris, P., 1987, In vitro and in vivo immunomodulatory activity of an N-9 arginyl hypoxantine derivative (PCF-39) Int J Immunopharmacol 9: 659–667.
Goldstein, A. L., Low, T.L.K., Mc Adoo, M., 1977, Thymosin alpha 1. Isolation and seuence analysis of an immunological active thymic polypeptide, Proc Natl Acad Sci USA 74: 711–715.
Hirano, T., Akira, S., Taga, T., Kishimoto, T., 1990, Biological and clinical aspects of interleukin 6, Immunol Today 11: 443–449.
Isidori, A., Lo Monaco, A., Cappa, M., 1981, A study of growth hormone release in man after oral administration of amino acids, Curr Med Opin 7: 475–481.
Keller, R., Geiges, M., Keist, R., 1990, L-arginine-dependent reactive intermediates as mediator of tumor cell killing by activated macrophages, Cancer Res 50: 1421–1425.
Kishimoto, T., 1989, The biology of interleukin-6, Blood 74: 1–10.
Lowell, J. A., Fames, H. L., Blackborn, G. L., 1990, Dietary immunomodulation: beneficial effects on oncogenesis and tumor growth, Crit Care Med 18: 145–148.
Matsumoto, M., Matsubara, S., Matsuno, T., 1987, Protective effect of human granulocyte colony-stimulating factor on microbial infections in neutropenic mice, Infect Immunol 55: 2715–2722.
Munno, I., Pellegrino, N. M., Marcuccio, C., De Simone, C., Jirillo, E., 1991 (in press) Influence of ST 789 on interleukin-1, interleukin-2 and interferon-gamma production from normal human peripheral blood mononuclear cells, Thymus.
Ponzoni, M., Cirillo, C., Perezzani, L. S., Comaglia-Ferraris, P., 1987, Immunomodulatory properties of a new hypoxantine derivative, PCF-39. II. Comparison with other agents promoting the differentiation of human myeloid or monocyte-like cell lines, EOS J Immunol Immunopharmacol 7: 166–171.
Reynolds, J. V., Daly, J. M., Zhang, S. M., Ziegler, M. M., Nasi, A., 1988, Arginine, protein malnutrition and cancer, J Surgery Res 45: 513–522.
Reynolds, J. V., Daly, J. M., Shou, J., Sigal, R., Ziegler, M. M., Naji,A., 1990, Immunological effects of arginine supplementation in tumor bearing and non tumor-bearing hosts. Ann Surg 211: 202–210.
Riccardi, C., Migliorati, G., 1991 (in press), Enhancement of murine NK cell activity generation by ST 789, Thymus.
Ruggiero, V., Albertoni, C., Manganello, S., Foresta, P., Arrigoni-Martelli E., 1991 (in press), Modulation of splenic lymphocyte activities by a new hypoxantine derivative (ST 789) in immunosuppressed mice, Agents Act.
Seifter, E., Rettura, G., Barbui, A., Levenson, S. M., 1978, Arginine: an essential aminoacid for injured rats, Surgery 84: 224–230.
Stradi, R., Rossi, E., Perezzani, L., Migliorati, G., Riccardi, C., Cornaglia-Ferraris, P., 1990, Synthetic biological response modifiers.Part I. Synthesis and immunomodulatory properties of some N2-(w-(hypoxanthin-9-YL)alkoxycarbonyl)-L-arginines, Il Farmaco 45: 39–47.
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© 1992 Springer Science+Business Media New York
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De Simone, C. et al. (1992). ST 789, A Candidate for Combination Therapies of Infections and Cancer. In: Goldstein, A.L., Garaci, E. (eds) Combination Therapies. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3340-5_27
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DOI: https://doi.org/10.1007/978-1-4615-3340-5_27
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-6472-6
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