Skip to main content
Cancer Immunology, Immunotherapy : CII logoLink to Cancer Immunology, Immunotherapy : CII
. 1991 Sep;32(5):311–314. doi: 10.1007/BF01789049

No inhibition of interferon γ release in human lymphocytes by Ciamexone

J Baier 1,, H A Neumann 1, O Ricken 1
PMCID: PMC11038928  PMID: 1900217

Abstract

In previous experiments Ciamexone, derivative of 2-cyan-aziridine, was able to influence T-cell-mediated regulatory mechanisms but seemed to have no or only little effect on T cell effector mechanisms. On the basis of these observations Ciamexone seems to be a highly selective immunosuppressive agent. In order to evaluate further possible mechanisms of Ciamexone it was the aim of our investigation to study its influence on interferon γ (IFNγ) production in phytohaemogglutinin (PHA)-stimulated T lymphocytes of 15 tumour patients and 12 healthy reference subjects. The IFNγ concentration of the cell supernatant was measured using an enzyme-linked immunosorbent assay. When the cells were stimulated with PHA at 7.5 µg/ml the IFNγ concentration rose to significantly different values in the reference group (1.0 ng/ml) as compared to the tumour patients (0.4 ng/ml) (P <0.05). An addition of Ciamexone (at any of the concentrations administered) to PHA stimulation of peripheral blood mononuclear cells (PBMC) showed no influence on the IFNγ release in either test group. The influence of hydrocortisone on the stimulation of PBMC with PHA resulted in a dose-dependent suppression of IFNγ production in both test groups, again with significant differerences between them. The IFNγ concentration was 0.95 ng/ml in the reference group and 0.2 ng/ml in the tumour patients when 0.01 µg/ml hydrocortisone was added (P <0.05). At 10 µg/ml hydrocortisone suppressed IFNγ production completely in both groups. Our results corroborate those investigations that showed no influence of the compound on T cell effector mechanisms. The attenuation of humoral immunophenomena, however, suggest a very specific point of action within the immune system by Ciamexone.

Keywords: Hydrocortisone, Interferon, Peripheral Blood Mononuclear Cell, Reference Group, Specific Point

References

  • 1.Balkwill FR. Antitumor effects of interferons in animals. In: Finter NB, Oldham RK, editors. Interferon, Vol 4: In vivo and Clinical Studies. Amsterdam: Elsevier; 1985. p. 23. [Google Scholar]
  • 2.Bicker U, Fuhse P. Carcinostatic action of 2-cyan-aziridine against sarcoma in rats. Exp Pathol. 1974;10:279. doi: 10.1016/s0014-4908(75)80034-2. [DOI] [PubMed] [Google Scholar]
  • 3.Bicker U, Pahlke W. Ciamexone — a new highly selective immunosuppresive compound. J Immunopharmacol. 1985;7:127. doi: 10.3109/08923978509026474. [DOI] [PubMed] [Google Scholar]
  • 4.Bicker U, Usadel KG. Ciamexone, a highly selective immunomodulator — a tool for autoimmune diseases? Klin Wochenschr. 1986;64:1261. doi: 10.1007/BF01785706. [DOI] [PubMed] [Google Scholar]
  • 5.Bocci V. The physiological interferon response. Immunol Today. 1985;6:7. doi: 10.1016/0167-5699(85)90159-8. [DOI] [PubMed] [Google Scholar]
  • 6.Boehringer Mannheim GmbH (1986) Exposé Ciamexone
  • 7.Chirigos MA, Schlick E, Saito T, Gruys E. Biological response modifiers: regulators of the cellular immune system and adjuvant in antitumor therapy. Methods Find Exp Clin Pharmacol. 1986;8:27. [PubMed] [Google Scholar]
  • 8.Friedman RM. Antiviral activity of interferon. Bacteriol Rev. 1977;41:543. doi: 10.1128/br.41.3.543-567.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Gallati H, Pracht I, Schmidt J, Häring P, Garotta G. A simple rapid and large capacity ELISA for biologically active native and recombinant human IFN-gamma. J Biol Regul Homeostatic Agents. 1987;1:109. [PubMed] [Google Scholar]
  • 10.Gresser I (1985) How does interferon inhibit tumor growth? Interferon 6: [PubMed]
  • 11.Isaacs A, Lindenmann B. Virus interference: the interferon. Proc Ro Soc Lond [Biol] 1957;147:258. [PubMed] [Google Scholar]
  • 12.Johnston MI, Torrence PF. The role of interferon-induced proteins, double stranded RNA and 2′5′-oligo-adenylate in the interferon-mediated inhibition of viral translation. In: Friedman RM, editor. Interferon, vol 3: Mechanisms of production and action. Amsterdam: Elsevier; 1984. p. 47. [Google Scholar]
  • 13.Kadota K, Okuda T, Skamoto K, Nishikaku F, Yoshihiko K (1986) Pharamcological investigation of ciamexone (BM 41.332) Sumitomo Pharmaceuticals Co. Ltd. SRD 01788 reports
  • 14.Kahaly G, Bockmann H, Cordes U, Beyer J. Langzeitbeobachtung der endokrinen Ophthalmopathie und retrospektive Beurteilung therpeutischer Maßnahmen. Med Klin. 1989;84:121. [PubMed] [Google Scholar]
  • 15.Kirchner H. Interferons. A group of multiple lymphokines. Springer Semin Immunopathol. 1984;7:347. doi: 10.1007/BF00201966. [DOI] [PubMed] [Google Scholar]
  • 16.Kirchner H. Das Interferonsystem unter besonderer Berücksichtigung von Gamma-Interferon. Dtsch Med Wochenschr. 1986;111:64. doi: 10.1055/s-2008-1068404. [DOI] [PubMed] [Google Scholar]
  • 17.Kohler E, Knospe S, Hahn HJ, Roemer KG, Diamantstein T. Ciamexone suppressed anti-islet ADCC of mononuclear cells and serum from type 1 (insulin dependent) diabetic patients. Exp Clin Endocrinol. 1989;93:143. doi: 10.1055/s-0029-1210847. [DOI] [PubMed] [Google Scholar]
  • 18.Langer JA, Pestka S. Structure of interferons. Pharmacol Ther. 1985;27:371. doi: 10.1016/0163-7258(85)90076-2. [DOI] [PubMed] [Google Scholar]
  • 19.Murray HW, Rubin BY, Masur H, Roberts RB. Impaired production of lymphokines and immune (gamma) interferon in the acquired immunodeficiency syndrome. N Engl J Med. 1984;310:883. doi: 10.1056/NEJM198404053101404. [DOI] [PubMed] [Google Scholar]
  • 20.Nussenblatt RB, Gery I, Ballintine RJ, Wacker WB. Cellular immune of uveitis patients to retinal S-antigen. Am J Ophthalmol. 1980;89:173. doi: 10.1016/0002-9394(80)90108-7. [DOI] [PubMed] [Google Scholar]
  • 21.Paganelli R, Capobianchi MR, Matricardi PM, Cloe L, Seminara R, Dianzani F, Aiuti F. Defective interferon-gamma production in ataxia-teleangiectatica. Clin Immunol Immunopathol. 1984;32:387. doi: 10.1016/0090-1229(84)90282-4. [DOI] [PubMed] [Google Scholar]
  • 22.Pestka S. The human interferons — from protein purification and sequence ot cloning and expression in bacteria: before, between and beyond. Arch Biochem Biophys. 1983;221:1. doi: 10.1016/0003-9861(83)90118-2. [DOI] [PubMed] [Google Scholar]
  • 23.Revel M, Chebath J. Interferon-activated genes. Trends Biochem Sci. 1986;11:166. [Google Scholar]
  • 24.Ross F, Fellous M. The effect of gamma-interferon on MHC antigens. Immunol Today. 1984;5:261. doi: 10.1016/0167-5699(84)90135-X. [DOI] [PubMed] [Google Scholar]
  • 25.Samid D, Chang EH, Friedman RM. Biochemical correlations of phenotypic reversion in interferon-treated mouse cells transformed by a human oncogene. Biochem Biophys Res Commun. 1984;119:21. doi: 10.1016/0006-291x(84)91612-7. [DOI] [PubMed] [Google Scholar]
  • 26.Sehgal PB, Pheffer LM, Tam I. Interferons and its inducers. In: Carne PW, Caliguin LA, editors. Chemotherapy of viral infections. Berlin, Heidelberg, New York: Springer; 1982. [Google Scholar]
  • 27.Stewart WE., II . The interferon system. Berlin, Heidelberg, New York: Springer Verlag; 1979. [Google Scholar]
  • 28.Taylor-Papadimitriou J. Effects of interferons on cell growth and function. In: Billiau A, editor. Interferon, vol 1: General and applied aspects. Amsterdam: Elsevier; 1984. [Google Scholar]
  • 29.Vilcek J. Interferon production and its regulation. In: Friedman RM, editor. Interferon, vol 3: Mechanisms of production and action. Amsterdam: Elsevier; 1984. p. 1. [Google Scholar]
  • 30.Vilcek J, Kelker HC, Jumming L, Yip Y. Structure and function of human interferon gamma. In: Ford JR, Abby LM, editors. Mediators in cell growth and differentiation. New York: Raven; 1985. [Google Scholar]
  • 31.Vilcek J, Klion A, Hendriksen-Destefano D, Zemtsov A, Davidson DM, Davidson M, Friedman-Kien AE, Le J. Defective gamma-interferon production in peripheral blood leukocytes of patients with acute tuberculosis. J Clin Immunol. 1986;6:146. doi: 10.1007/BF00918747. [DOI] [PubMed] [Google Scholar]
  • 32.Yap WH, Teo TS, Tan Yh. An early event in the interferon-induced transmembrane signaling process. Science. 1986;234:355. doi: 10.1126/science.2429366. [DOI] [PubMed] [Google Scholar]
  • 33.Young HA, Ortaldo JR. One-signal requirement for interferon-production by human large granular lymphocytes. J Immunol. 1987;139:724. [PubMed] [Google Scholar]
  • 34.Zoon KC, Arnheiter H. Studies of the interferon receptors. Pharmacol Ther. 1984;24:259. doi: 10.1016/0163-7258(84)90037-8. [DOI] [PubMed] [Google Scholar]

Articles from Cancer Immunology, Immunotherapy : CII are provided here courtesy of Springer

RESOURCES