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FCE 20696, a new synthetic immunomodulator: Immunopharmacological profile

  • Inflammation and Immunomodulation
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Abstract

A preliminary characterization of the immunopharmacological profile of the new immunomodulating agent FCE 20696 (6H,6 [2-(dimethylamino)-ethoxycarbonyl]-dibenzo[b,d]pyran-HCl) was performed in mice.

Single i.p. doses of this chemical, concomitantly given with the antigen, increased the antibody response and decreased the delayed hypersensitivity reaction to a suboptimal dose of SRBC, the active doses ranging from 6.25 to 50 mg/kg. No activity was observed using a full antigen dose. Macrophage cytotoxic activity was enhanced 2–4 days after a single i.p. treatment with 50 and 10 mg/kg. Spleen cell proliferation to T and B mitogens was inhibited by a single dose of 30 mg/kg given i.p. 6 days before the test, or by 10 mg/kg×3 days ending one day before the test. Finally, generation of suppressor cells was enhanced by the compound, given p.o. biweekly for at least 7 weeks, at doses ranging from 0.1 to 10 mg/kg. Collectively taken, these data suggest that FCE 20696 has a broad range of immunomodulating activities and that macrophages and suppressor cells are presumed to be the main targets of its pharmacological activity.

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Abbreviations

SRBC:

sheep red blood cells

DH:

delayed hypersensitivity

MTT:

(3-(4,5-dimethylthiazol-1-yl)-2,5-diphenyl tetrazolium bromide)

Con A:

concanavalin A

PHA:

phytohemagglutinin

LPS:

lipopolysaccharide

CCA:

N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt

[3H]TdR:

methyl-3H-Thymidine

CNS:

central nervous system

References

  1. J. W. Hadden and F. Spreafico,New strategies in Immunotherapy. Springer Semin. Immunopathol.8, 321–326 (1985).

    PubMed  Google Scholar 

  2. A. M. Isetta, M. C. Fornasiero, M. Ferrari and D. Trizio,Activity of the immunomodulator FCE 20696 on experimental models of autoimmunity. Int. J. Immunopharmacol.7, 389 (1985).

    Google Scholar 

  3. M. A. Verini and D. Ungheri,FCE 20696, a new synthetic immunomodulator, activity in models of viral and bacterial pathology. Immunopharmacology, in press.

  4. I. Brandslund, H. C. Siersted, J. C. Jensensius and S. E. Svehag,Detection and quantitation of immune complexes with rapid polyethylene glycol precipitation complement consumption method. Methods in Enzymology vol. 74 (Eds. J. J. Langone and H. Van Vunakis) pp. 551–557, Academic Press, New York 1981.

    Google Scholar 

  5. P. H. Lagrange, G. B. Mackaness and T. E. Miller,Potentiation of T cell mediated immunity by selective suppression of antibody formation with cyclophosphamide. J. Exp. Med.139, 1529–1539 (1974).

    PubMed  Google Scholar 

  6. D. Boraschi, D. Soldateschi and A. Tagliabue,Macrophage activation by interferon; dissociation between tumoricidal capacity and suppressive activity. Europ. J. Immunol.12, 320–326 (1982).

    Google Scholar 

  7. T. Mosmann,Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assay. J. Immunol. Methods65, 55–63 (1983).

    PubMed  Google Scholar 

  8. D. Trizio, C. Della Bruna and A. M. Isetta,Modification of immune responsiveness in murine Schistosomiasis mansoni. I. Time course after cercarial exposure. Immunology40, 353–358 (1980).

    PubMed  Google Scholar 

  9. R. R. Rich and S. Solliday-Rich,Biological expression of lymphocyte activation. IV. Concanavalin A activated suppressor cells in mouse mixed lymphocyte reactions. J. Immunol.114, 1112–1115 (1975).

    PubMed  Google Scholar 

  10. L. Binderup,Decreased T-suppressor cell activity in rats with adjuvant arthritis. Ann. Rheum. Dis.42, 693–698 (1983).

    PubMed  Google Scholar 

  11. A. Ben Nun and I. R. Cohen.Spontaneous remission and acquired resistance to autoimmune encephalomyelitis (EAE) are associated with suppression of T cell reactivity: suppressed EAE effector cell recovered as T cell lines. J. Immunol.128, 1450–1457 (1982).

    PubMed  Google Scholar 

  12. J. S. Moore and C. E. Calkins,In vitro regulation of the pathogenic autoantibody response of New Zealand Black mice. I. Loss with age of suppressive activity in T cell populations. J. Immunol.134, 3838–3845 (1985).

    PubMed  Google Scholar 

  13. D. O. Adams and A. T. Hamilton,The cell biology of macrophage activation. Annual Rev. Immunol.2, 283–318 (1984).

    Google Scholar 

  14. H. Kirchner, B. R. Fembach and R. B. Herberman,Macrophages suppressing T and B mitogen responses and the mixed leukocyte reaction. Mitogens in Immunology. (Eds. J. J. Oppenheim and D. L. Rosenstreich) pp. 495–507, Academic Press, New York 1976.

    Google Scholar 

  15. Z. Metzger, J. T. Hoffeld and J. J. Oppenheim,Macrophagemediated suppression. I. Evidence for partecipation of both hydrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. J. Immunol.124, 983–988 (1980).

    PubMed  Google Scholar 

  16. W. Ptak, M. Zembala, G. L. Asherson and J. Marcinkiewicz,Inhibition of contact sensitivity by macrophages. Int. Arch. Allergy Appl. Immunol.65, 121–126 (1981).

    PubMed  Google Scholar 

  17. L. Varesio and H. T. Holden,Suppression of lymphokine production. I. Macrophage-mediated inhibition of MIF production.Cell Immunol. 56, 16–28 (1980).

    PubMed  Google Scholar 

  18. A. Santoni, C. Riccardi, T. Barlozzari and R. B. Herbermann,Suppression of activity of mouse natural killer (NK) cells by activated macrophages from mice treated with pyran copolymer. Int. J. Cancer26, 837–845 (1980).

    PubMed  Google Scholar 

  19. R. M. Schultz, J. R. Schimidtke and A. G. Johnson,Role of macrophages in immunopotentiation by Adjuvants. The Reticuloendotelial System, vol. 6 (Eds. H. Friedman, M. Escobar and M. S. Reichard) pp. 319–337, Plenum Press, New York 1984.

    Google Scholar 

  20. M. A. Verini,Mechanism of antiviral activity of a new synthetic immunomodulator. Int. J. Immunopharmacol.7, 389 (1985).

    Google Scholar 

  21. M. C. Fornasiero, A. M. Isetta, M. Ferrari and D. Trizio,Antigen specific suppressor cells induced by the immunomodulator FCE 20696 in aged NZB/WF 1 mice. Agents and Actions19, 315–317 (1986).

    Google Scholar 

  22. T. Nakano, Y. Yamashita, Y. Ohsugi, Y. Sugawara, S. Hata and Y. Takagaki,The effect of CCA (Lobenzarit disodium) on the suppressor T cells function and the production of autoantibodies in New Zealand Black and New Zealand White F 1 mice. Immunopharmacology5, 293–302 (1983).

    PubMed  Google Scholar 

  23. I. Yamamoto, H. Ohmori and M. Sasano,CCA: an immunopharmacological profile “in vivo” and “in vitro”. Drugs Exptl. Clin. Res.1, 5–10 (1982).

    Google Scholar 

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Isetta, A.M., Fornasiero, M.C., Ferrari, M. et al. FCE 20696, a new synthetic immunomodulator: Immunopharmacological profile. Agents and Actions 28, 283–289 (1989). https://doi.org/10.1007/BF01967416

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