Skip to main content
SpringerLink
Log in

Effects of the immunomodulator diacetyl-splenopentin on antigen-induced arthritis in rabbits

  • Inflammation and Immunomodulation
  • Published:
Agents and Actions Aims and scope Submit manuscript

Abstract

Long-term treatment with the immunomodulator diacetyl-splenopentin reduces the severity of chronic joint inflammation and cartilage destruction in rabbits with antigen-induced arthritis. The level of specific antibodies as well as specific and non-specific cell-mediated immune reactivities including the proliferative response of spleen lymphocytes to cartilage proteoglycans in treated animals are lower than in untreated arthritic rabbits. Moreover, suppressor cell activity, which normally decreases during the early phase of inflammation, is enhanced and hyperreactive helper cell potential is reduced. These findings suggest that treatment with diacetyl-splenopentin normalizes the immune regulation, which is disturbed in the early phase of inflammation. This might result in a depression of the hyperreactive immune system including the autoimmunity developed against cartilage. Lowered immune reactivity in the joint in turn reduces the severity of chronic joint inflammation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. I. M. Hunneyball and D. R. Stanworth,Immunological models of rheumatoid arthritis with particular reference to the rabbit., IRCS J. Med. Sci.9, 1–4 (1981).

    Google Scholar 

  2. I. M. Hunneyball,Use of experimental arthritis in the rabbit for the development of antiarthritic drugs. Adv. Inflamm. Res.7, 249–262 (1984).

    Google Scholar 

  3. D. C. Dumonde and L. E. Glynn,The production of arthritis in rabbits by an immunological reaction to fibrin. Br. J. Exp. Pathol.43, 373–383 (1962).

    PubMed  Google Scholar 

  4. L. E. Glynn,The chronicity of inflammation and its significance in rheumatoid arthritis. Ann. Rheum. Dis.27, 105–121 (1968).

    PubMed  Google Scholar 

  5. M. E. Steinberg, C. R. McCrae, L. D. Cohen and H. R. Schumacher,Pathogenesis of antigen-induced arthritis. Clin. Orthop. Relat. Res.97, 248–260 (1973).

    PubMed  Google Scholar 

  6. V. M. Goldberg, E. M. Lange and P. Davis,Experimental immune synovitis in the rabbit. Relative role of cell mediated and humoral immunity. Arthritis Rheum.17, 993–1005 (1974).

    PubMed  Google Scholar 

  7. E. R. Pettipher and B. Henderson,The relationship between cell-mediated immunity and cartilage degradation in antigen-induced arthritis in the rabbit. Br. J. Exp. Pathol.69, 113–122 (1988).

    PubMed  Google Scholar 

  8. R. Bräuer, K. Thoss, S. Henzgen and G. Waldmann,Significance of cell-mediated and humoral immunity in the acute and chronic phase of antigen-induced arthritis in rabbits. Exp. Pathol.14, 197–208 (1988).

    Google Scholar 

  9. B. R. Champion and A. R. Poole,Immunity to homologous cartilage proteoglycans in rabbits with chronic inflammatory arthritis. Collagen Relat. Res.1, 453–473 (1981).

    Google Scholar 

  10. T. F. Kresina, I. A. Rosner, V. M. Goldberg and R. W. Moskowitz,Immunoglobulin G-induced experimental chronic immune synovitis: cell-mediated immunity to native interstitial collagen molecules and their constituent polypeptide chains. Cell. Immunol.87, 504–516 (1984).

    Article  PubMed  Google Scholar 

  11. J. U. Yoo, T. F. Kresina, C. J. Malemund and V. M. Goldberg,Epitopes of proteoglycans eliciting an anti-proteolgycan response in chronic immune synovitis. Proc. Nat. Acad. Sci. USA84, 832–836 (1987).

    PubMed  Google Scholar 

  12. T. F. Kresina, J. U. Yoo and V. M. Goldberg,Evidence that a humoral immune response to autologous cartilage proteoglycan can participate in the induction of cartilage pathology. Arthritis Rheum.31, 248–257 (1988).

    PubMed  Google Scholar 

  13. R. Bräuer, S. Henzgen, K. Thoss and G. Waldmann,Changes of immunoregulatory properties and induction of autoimmune reactivity to cartilage in rabbits with antigen-induced arthritis. Exp. Pathol.40, 35–44 (1990).

    PubMed  Google Scholar 

  14. G. Goldstein and T. K. Audhya,Thymopoietin to thymopentin: experimental studies. Survey Immunol. Res.4, suppl. 1, 1–10 (1985).

    Google Scholar 

  15. W. Diezel, R. Eckert, H.-D. Volk, S.-R. Goan, K. Forner, R. von Baehr, N. Sönnichsen and P. Oehme,Splenopentin-Biologische Wirkungen und therapeutische Aspekte. Z. Klin. Med.42, 15–18 (1987).

    Google Scholar 

  16. M. E. J. Billingham,Models of arthritis and the search for anti-arthritic drugs. Pharmacol. Ther.21, 389–428 (1983).

    Article  PubMed  Google Scholar 

  17. M. J. Crossley, M. Spowage and I. M. Hunneyball,Studies of the effects of pharmacological agents on antigen-induced arthritis in Balb/c mice. Drugs Exp. Clin. Res.13, 273–277 (1987).

    PubMed  Google Scholar 

  18. W. Diezel, R. Eckert, K. Forner and S. Gruner,Functional effects of splenin 32–34 on antibody formation in immunosuppressed mice. Biomed. Biochim. Acta10, 1349–1352 (1986).

    Google Scholar 

  19. R. Eckert, W. Diezel, K. Forner, U. Pfüller and R. von Baehr,Histamine receptor bearing lymphocytes (HRL): splenopentin-accelerated reconsitution of the immunoresponsiveness after elimination of HRL. All. Immunol.32, 267–270 (1986).

    Google Scholar 

  20. H. A. Weber, J. Maciejewski, R. Eckert, M. Schütt, W. Diezel and H.-D. Volk,Splenopentin (DAc-SP-5) accelerates the restoration of myelopoietic and immune systems after sublethal radiation in mice. Int. J. Immunopharmacol.12, 761–768 (1990).

    Article  PubMed  Google Scholar 

  21. E. M. Veys, E. C. Huskinsson, M. Rosenthal, T. L. Vischer, H. Mielants, P. A. Thrower, J. Scott, H. Ott, H. Scheijgrond and J. Symonens,Clinical response to therapy with thymopoietin pentapeptide (TP-5) in rheumatoid arthritis. Ann. Rheum. Dis.41, 441–443 (1982).

    PubMed  Google Scholar 

  22. M. Malaise, P. Franchimont, C. Hauwaert, B. Danneskiold-Samsoe, D. Gross, H. Gerber, H. Gerschpacher and K. Bolla,Interim results on the clinical effects of i.v. administered thymopentin in active rheumatoid arthritis. Int. J. Clin. Pharmacol. Res.4, 451–457 (1984).

    PubMed  Google Scholar 

  23. L. Molin, F. Schmid and K. Bolla,First observations on high-dosed and long-term thymopentin treatment in active rheumatoid arthritis. Int. J. Clin. Pharmacol. Res.4, 445–449 (1984).

    PubMed  Google Scholar 

  24. M. G. Malaise, C. Hauwaert, P. Franchimont, B. Danneskiold-Samsoe, R. Bach-Andersen, D. Gross, H. Gerber, H. Gerschpacher, H. Stocker and K. Bolla,Treatment of active rheumatoid arthritis with slow intravenous injections of thymopentin. A double-blind placebo-controlled randomised study. Lancet 1985/I, 832–836 (1985).

  25. L. Molin, F. Schmid and K. Bolla,Some observations on various dose regimens of thymopentin treatment in rheumatoid arthritis. Survey Immunol. Res.4, suppl. 1, 76–80 (1985).

    Google Scholar 

  26. E. M. Lemmel, G. L. Bach, W. Bolten, D. Brackertz, Z. Fahmy, H. Mattern, I. Stroehmann and A. Wittenborg,Immunmodulierende Therapie der chronischen Polyarthritis mit Thymopentin. Eine multizentrische placebokontrollierte Studie an 119 Patienten. Dtsch. med. Wschr.113, 172–176 (1988).

    PubMed  Google Scholar 

  27. G. Bodini, A. Luisa and A. Quadri,Clinical effects of thymopentin (Timunox) in patients with active rheumatoid arthritis. Int. J. Immunother.5, 129–131 (1989).

    Google Scholar 

  28. E. M. Veys, P. Hermanns, G. Goldstein, P. Kung, J. Schindler and J. van Wauwe,Determination of T lymphocyte subpopulations by monoclonal antibodies in rheumatoid arthritis. Influence of immunomodulating agents. Int. J. Immunopharmacol.3, 313–319 (1981).

    Article  PubMed  Google Scholar 

  29. E. M. Veys, H. Mielants, G. Verbruggen, T. Spiro, E. Newdeck, D. Power and G. Goldstein,Thymopoietein pentapeptide (thymopentin, TP-5) in the treatment of rheumatoid arthritis. A compilation of several short- and longterm clinical studies. J. Rheumatol.11, 462–466 (1984).

    PubMed  Google Scholar 

  30. M. Bardare, F. Corona, M. T. Ogliari and E. Cohen,Thymopentin in the treatment of juvenile chronic arthritis. Clin. Exp. Rheumatol.8, 89–93 (1990).

    Google Scholar 

  31. R. Colle, T. Ceschia, A. Colatutto and F. Biffoni,Use of thymopentin in autoimmune hemolytic anemia due to chronic lymphocytic leukemia. Curr. Therap. Res.44, 1045–1049 (1988).

    Google Scholar 

  32. M. G. Bernengo, G. C. Doveil, M. Meregalli, A. Appino and R. Massobrio,Immunomodulation and Sèzary syndrome: experience with thymopentin (TP-5). Br. J. Dermatol.119, 207–221 (1988).

    PubMed  Google Scholar 

  33. J. DeMaubeuge, E. Haneke, D. Djawari, K. Wolff, G. Stingl, L. Molin, E. Schöpf, R. Stengel, H. Degreef, E. Panconesi, B. Wüthrich and K. Bolla,Thymopentin treatment in Herpes simplex infection: an open, monitored, multicenter study. Survey Immunol. Res.4, suppl. 1, 30–36 (1985).

    Google Scholar 

  34. M. B. Sztein and A. L. Goldstein,Thymic hormones — a clinical update. Springer Semin. Immunopathol.9, 1–18 (1986).

    Article  PubMed  Google Scholar 

  35. S. Kato and H. Nakamura,Suppression of acute experimental allergic encephalomyelitis by synthetic serum thymic factor. Clinical, histopathological, and immunohistochemical studies. Acta Neuropathol.75, 337–344 (1988).

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, Friedrich Schiller University, O-6900, Jena, Federal Republik of Germany

    R. Bräuer, K. Thoss, S. Henzgen & G. Waldmann

Authors
  1. R. Bräuer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. K. Thoss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. S. Henzgen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Waldmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bräuer, R., Thoss, K., Henzgen, S. et al. Effects of the immunomodulator diacetyl-splenopentin on antigen-induced arthritis in rabbits. Agents and Actions 35, 96–103 (1992). https://doi.org/10.1007/BF01990958

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01990958

Keywords

Search

Navigation