CIMETIDINE ENHANCES INTERFERON INDUCED AUGMENTATION OF NK CELL ACTIVITY AND SUPPRESSES INTERFERON PRODUCTION
NOBUYUKI HIRAI
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
The First Department of Internal Medicine, School of Medicine, Kanazawa University, 13–1 Takaramachi, Kanazawa-shi, Ishikawa 920, Japan
Search for more papers by this authorNORWOOD O. HILL
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
Search for more papers by this authorYOSHIHARU MOTOO
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
Search for more papers by this authorCorresponding Author
KURT OSTHER
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
Blood Center at Wadley, 9000 Harry Hines Boulevard, Dallas, Texas 75235, U.S.ASearch for more papers by this authorNOBUYUKI HIRAI
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
The First Department of Internal Medicine, School of Medicine, Kanazawa University, 13–1 Takaramachi, Kanazawa-shi, Ishikawa 920, Japan
Search for more papers by this authorNORWOOD O. HILL
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
Search for more papers by this authorYOSHIHARU MOTOO
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
Search for more papers by this authorCorresponding Author
KURT OSTHER
Wadley Institutes of Molecular Medicine, Dallas, Texas, U.S.A.
Blood Center at Wadley, 9000 Harry Hines Boulevard, Dallas, Texas 75235, U.S.ASearch for more papers by this authorAbstract
Effects of cimetidine on the augmentation of natural killer (NK) cell activity by human leukocyte interferon (Hu IFN-α (Le)) and on the IFN production from donor leukocytes were investigated in virtro. NK cell activity of PBL was suppressed after 16 hours pretreatment with 0.3, 3.0, and 30.0 μg/ml of cimetidine. On the other hand, there was dose dependent suppression of Hu IFN-α (Le) production in PBL by cimetidine. The NK cell activity of PBL augmented by Hu IFN-α (Le) was further enhanced when the effector cells were pretreated with cimetidine or when cimetidine was added together with IFN. K562, G361, and PLC/PRF/5 cells were used as target cells. Our results suggest that a 16 hour treatment with cimetidine alone may suppress NK cell activity of PBL, probably due to reduced IFN production by leukocytes. On the other hand, cimetidine may enhance the IFN induced NK augmentation in PBL in vitro.
REFERENCES
- 1 Adams, A., Strander, H. & Cantell, K.: Sensitivity of the Epstein-Barr virus transformed human lymphoid cell lines to interferon. J. Gen. Virol. 28: 207–217, 1975.
- 2 Andersson, L. C., Jokinen, M. & Gahmberg, C. G.: Induction of erythroid differentiation in the human leukaemia cell line K562. Nature (Lond.) 278: 364–365, 1979.
- 3 Armitage, J. O. & Sidner, R. D.: Antitumor effect of cimetidine. Lancet 1: 882–883, 1979.
- 4 Bloom, B. R.: Interferons and the immune system. Nature (Lond.) 284: 593–595, 1980.
- 5 Borgström, S., Eyben, F.E., Flodgren, P., Axelsson, B. & Sjögren, H. O.: Human leukocyte interferon and cimetidine for metastatic melanoma. N. Engl. J. Med. 307: 1080–1081, 1982.
- 6 Brunner, K. T., Engers, H. D. & Cerrotinni, J. C.: In: B. R. Bloom & P. R. Glade (Eds.): In vitro methods of cell-mediated immunity, Academic Press, New York 1976, pp. 423–428.
- 7 Cantell, K., Hirvonen, S., Kauppinen, H. L. & Myllylä, G.: Production of interferon in human leukocytes from normal donors with use of Sendai virus. Methods Enzymol. 78: 29–38, 1981.
- 8 Djeu, J. Y., Heinbaugh, J. A., Holden, H. T. & Herberman, R. B.: Augmentation of mouse natural killer cell activity by interferon and interferon inducers. J. Immunol. 122: 175–181, 1979.
- 9 Freston, J. W.: Cimetidine. I. Developments, pharmacology, and efficacy. Ann. Intern. Med. 97: 573–580, 1982.
- 10 Freston, J. W.: Cimetidine in the treatment of gastric ulcer; review and commentary. Gastroenterology 74: 426–430, 1978.
- 11 Gifford, R. R. M., Voss, B. V. & Ferguson, R. M.: Cimetidine protection against lethal tumor challenge in mice. Surgery 90: 344–351, 1981.
- 12 Gifford, R. R. M., Gamble, C. E., Schmidtke, J. R. & Ferguson, R. M.: Cimetidine augmentation in vitro generated cell-mediated cytotoxicity. Surg. Forum 31: 379–382, 1980.
- 13 Gresser, I.: Effects of interferon in vivo. In: E. De-Maeyer, G. Galasso, & H. Schellekens (Eds.): Biology of the Interferon System, North Holland Biomedical Press, Amsterdam New York Oxford 1981, pp. 141–147.
- 14 Herberman, R. B., Djeu, J. Y., Fagnani, R., Santoni, A. & Puccetti, P.: Natural killer cells: characteristics and regulation of activity. Immunological Rev. 44: 43–70, 1979.
- 15 Herberman, R. B.: Natural killer cells. Hospital Practice 17: 93–103, 1982.
- 16 Heron, I., Hokland, M., Møller-Larsen, A. & Berg, K.: The effect of interferon on lymphocyte-mediated effector cell-functions: selective enhancement of natural killer cells. Cell. Immunol. 42: 183–187, 1979.
- 17 Hill, N. O., Pardue, A., Khan, A., Hill, R. W., Aleman, C., Hilario, R., Hill, J. M. & Osther, K.: Interferon and cimetidine for malignant melanoma. N. Engl. J. Med. 308: 286, 1983.
- 18 Hirai, N., Hill, N. O., Motoo, Y. & Osther, K.: Antiviral and antiproliferative activities of human leukocyte interferon potentiated by cimetidine in vitro. In press. J. Interferon Res.
- 19 Jorizzo, J. L., Sams, W. M., Jegasthy, B. V. & Olansky, A. J.: Cimetidine as an immunomodulator: chronic mucocutaneous candidiasis as a model. Ann. Intern. Med. 92: 192–195, 1980.
- 20 Láng, I., Török, K., Gergely, P., Nékám, K. & Petrányi, G. Y.: Effect of histamine receptor blocking on human antibody-dependent cell-mediated cytotoxicity. Scand. J. Immunol. 13: 361–366, 1981.
- 21 Láng, I., Gergely, P. & Petrányi, G. Y.: Effect of histamine receptor blocking on human spontaneous lymphocyte-mediated cytotoxicity. Scand. J. Immunol. 14: 573–576, 1981.
- 22 Leanderson, T. & Lundgren, E. J.: Growth inhibition by IFN achieved by collecting cells in GO. J. Interferon Res. 2: 21–29, 1982.
- 23 Lutz, W.: Statistical methods as applies to immunological data. In: D. M. Weir, (Ed.): Handbook of Experimental Immunology, Vol. 3, Alden Press, Oxford 1978, A-2, pp. 1–20.
- 24 MacNab, G. M., Alexander, J. J., Lecatsas, G., Bey, E. M. & Urbanowicz, J. M.: Hepatitis B surface antigen produced by a human hepatoma cell line. Br. J. Cancer 34: 509–515, 1976.
- 25 Meretey, K., Room, G. & Maini, R. N.: Effect of histamine on the mitogenic response of human lymphocytes and its modification by cimetidine and levamisole. Agents and Actions 11: 84–88, 1981.
- 26 Ogden, B. E. & Hill, H. R.: Histamine regulates lymphocyte mitogenic responses through activation of specific H1 and H2 histamine receptors. Immunology 41: 107–114, 1980.
- 27 Osband, M. E., Hamilton, D., Shen, Y.J., Cohen, E., Shlesinger, M., Lavin, P., Brown, A. & MacCaffrey, R.: Successful tumour immunotherapy with cimetidine in mice. Lancet 1, March 21: 636–638, 1981.
- 28 Peebles, P. T., Trisch, T., & Papageorge, A. G.: Isolation of 4 unusual pediatric solid tumor cell lines. Pediatric Research 12: 485, 1978.
- 29 Plaut, M., Lichenstein, L. M. & Henney, C. S.: Properties of a sub-population of T cells bearing Histamine receptors. J. Clin. Invest. 55: 856–874, 1975.
- 30 Plaut, M., Lichenstein, L. M., Gillespie, E. & Henney, C. S.: Studies on the mechanism of lymphocyte-mediated cytolysis. IV. Specificity of the histamine receptor on effector T cells. J. Immunol. 111: 389–394, 1973.
- 31 Ruiz-Argüelles, A., Serrogy, K. B. & Ritts, R. E., Jr.: In vitro effect of cimetidine on human cell-mediated cytotoxicity. I. Inhibition of natural killer cell activity. Cell. Immunol. 69: 1–12, 1982.
- 32 Saksela, E., Timonen, T. & Cantell, K.: Human natural killer cell activity is augmented by interferon via recruitment of ‘Pre-NK’ cells. Scand. J. Immunol. 10: 257–266, 1979.
- 33 Siegel, J. N., Schwartz, A., Askenase, P. W. & Gershon, R. K.: T-cell suppression and contrasuppression induced by histamine H2 and H1 receptor agonists, respectively. Proc. Natl. Acad. Sci. USA. 79: 5052–5056, 1982.
- 34
Stewart, II, W. E.: Non antiviral actions of interferons. In: The Interferon System, Springer-Verlag,
Wien
,
New York
1979, pp.
223–256.
10.1007/978-3-7091-3432-0_10 Google Scholar
- 35 Sawyer, D., Conner, C. S. & Scalley, R.: Cimetidine: adverse reactions and acute toxicity. Am J. Hosp. Pharm. 38: 188–197, 1981.
- 36 Trinchieri, G. & Santoli, D.: Enhancement of natural killer cell activity by interferon. J. Exp. Med. 147: 1314–1333, 1978.
- 37 Trinchieri, G., Santoli, D. & Knowles, B. B.: Tumour cell lines induce interferon in human lymphocytes. Nature (Lond.) 270: 611–613, 1977.
- 38 Tutton, P. J. M. & Barkla, D. H.: Comparison of the tumor inhibiting effects of three histamine H2 receptor antagonists. Anticancer Res. 3: 7–10, 1983.
- 39 Winship, D. H.: Cimetidine in the treatment of duodenal ulcer: review and commentary. Gastroenterology 74: 402–406, 1978.
