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. 1995 Oct;102(1):85–90. doi: 10.1111/j.1365-2249.1995.tb06640.x

Potentiation of in vitro synthesis of human IgE by cyclosporin A (CsA).

D J Wheeler 1, A Robins 1, D I Pritchard 1, R V Bundick 1, F Shakib 1
PMCID: PMC1553346  PMID: 7554405

Abstract

In this study, we investigated the modulatory effects of CsA on in vitro synthesis of IgE, IgG1 and IgG4 by human peripheral blood mononuclear cells (PBMC). In contrast to its known immunosuppressive effect, we have demonstrated that a low dose of CsA (10(-7) M, 120 ng/ml) potentiated IgE production by up to 40-fold (i.e. from 33 +/- 4.5 to 1346 +/- 290 ng/ml). This potentiation was specific for IgE since no such effect was demonstrable with IgG1 and IgG4. Potentiation of IgE synthesis by CsA in the PBMC cultures was partly due to CsA acting on T cells, as demonstrated by the addition of CsA-treated T cells to T cell-depleted cultures. However, potentiation was also demonstrable in a T cell-depleted, anti-CD40-stimulated culture (four-fold increase from 400 +/- 48 to 1606 +/- 127 ng/ml). Our data therefore suggest that there are at least two mechanisms for CsA-induced potentiation of IgE synthesis, one T cell-dependent and the other T cell-independent. The clinical implications of these findings are discussed with regard to the use of CsA in the treatment of Th2-mediated diseases.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander A. G., Barnes N. C., Kay A. B. Trial of cyclosporin in corticosteroid-dependent chronic severe asthma. Lancet. 1992 Feb 8;339(8789):324–328. doi: 10.1016/0140-6736(92)91646-p. [DOI] [PubMed] [Google Scholar]
  2. Bach J. F. Cyclosporine in autoimmune diseases. Transplant Proc. 1989 Jun;21(3 Suppl 1):97–113. [PubMed] [Google Scholar]
  3. Brynskov J., Freund L., Rasmussen S. N., Lauritsen K., de Muckadell O. S., Williams N., MacDonald A. S., Tanton R., Molina F., Campanini M. C. A placebo-controlled, double-blind, randomized trial of cyclosporine therapy in active chronic Crohn's disease. N Engl J Med. 1989 Sep 28;321(13):845–850. doi: 10.1056/NEJM198909283211301. [DOI] [PubMed] [Google Scholar]
  4. Casolaro V., Spadaro G., Patella V., Marone G. In vivo characterization of the anti-inflammatory effect of cyclosporin A on human basophils. J Immunol. 1993 Nov 15;151(10):5563–5573. [PubMed] [Google Scholar]
  5. Chang C. C., Aversa G., Punnonen J., Yssel H., de Vries J. E. Brequinar sodium, mycophenolic acid, and cyclosporin A inhibit different stages of IL-4- or IL-13-induced human IgG4 and IgE production in vitro. Ann N Y Acad Sci. 1993 Nov 30;696:108–122. doi: 10.1111/j.1749-6632.1993.tb17146.x. [DOI] [PubMed] [Google Scholar]
  6. Chen S. S., Li Q., Pearlman E., Chen W. H. Dual mechanisms of potentiation of murine antigen-specific IgE production by cyclosporin A in vitro. J Immunol. 1992 Aug 1;149(3):762–767. [PubMed] [Google Scholar]
  7. Chen S. S., Stanescu G., Magalski A. E., Qian Y. Y. Cyclosporin A is an adjuvant in murine IgE antibody responses. J Immunol. 1989 Jun 15;142(12):4225–4232. [PubMed] [Google Scholar]
  8. Ellis C. N., Fradin M. S., Messana J. M., Brown M. D., Siegel M. T., Hartley A. H., Rocher L. L., Wheeler S., Hamilton T. A., Parish T. G. Cyclosporine for plaque-type psoriasis. Results of a multidose, double-blind trial. N Engl J Med. 1991 Jan 31;324(5):277–284. doi: 10.1056/NEJM199101313240501. [DOI] [PubMed] [Google Scholar]
  9. Gajewski T. F., Schell S. R., Fitch F. W. Evidence implicating utilization of different T cell receptor-associated signaling pathways by TH1 and TH2 clones. J Immunol. 1990 Jun 1;144(11):4110–4120. [PubMed] [Google Scholar]
  10. Gascan H., Gauchat J. F., Roncarolo M. G., Yssel H., Spits H., de Vries J. E. Human B cell clones can be induced to proliferate and to switch to IgE and IgG4 synthesis by interleukin 4 and a signal provided by activated CD4+ T cell clones. J Exp Med. 1991 Mar 1;173(3):747–750. doi: 10.1084/jem.173.3.747. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Glazier A., Tutschka P. J., Farmer E. R., Santos G. W. Graft-versus-host disease in cyclosporin A-treated rats after syngeneic and autologous bone marrow reconstitution. J Exp Med. 1983 Jul 1;158(1):1–8. doi: 10.1084/jem.158.1.1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ishizaka A., Sakiyama Y., Nakanishi M., Tomizawa K., Oshika E., Kojima K., Taguchi Y., Kandil E., Matsumoto S. The inductive effect of interleukin-4 on IgG4 and IgE synthesis in human peripheral blood lymphocytes. Clin Exp Immunol. 1990 Mar;79(3):392–396. doi: 10.1111/j.1365-2249.1990.tb08101.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Jones R. J., Vogelsang G. B., Hess A. D., Farmer E. R., Mann R. B., Geller R. B., Piantadosi S., Santos G. W. Induction of graft-versus-host disease after autologous bone marrow transplantation. Lancet. 1989 Apr 8;1(8641):754–757. doi: 10.1016/s0140-6736(89)92575-0. [DOI] [PubMed] [Google Scholar]
  14. Kahan B. D. Cyclosporine. N Engl J Med. 1989 Dec 21;321(25):1725–1738. doi: 10.1056/NEJM198912213212507. [DOI] [PubMed] [Google Scholar]
  15. Kim H. S., Raskova J., Degiannis D., Raska K., Jr Effects of cyclosporine and rapamycin on immunoglobulin production by preactivated human B cells. Clin Exp Immunol. 1994 Jun;96(3):508–512. doi: 10.1111/j.1365-2249.1994.tb06058.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Luo H. Y., Chen H. F., Daloze P., Chang J., St-Louis G., Wu J. P. In vitro IgE production by interleukin 4-stimulated human peripheral blood mononuclear cells is suppressed by rapamycin. Clin Immunol Immunopathol. 1991 Dec;61(3):410–420. doi: 10.1016/s0090-1229(05)80012-1. [DOI] [PubMed] [Google Scholar]
  17. Munro C. S., Higgins E. M., Marks J. M., Daly B. M., Friedmann P. S., Shuster S. Cyclosporin A in atopic dermatitis: therapeutic response is dissociated from effects on allergic reactions. Br J Dermatol. 1991 Jan;124(1):43–48. doi: 10.1111/j.1365-2133.1991.tb03280.x. [DOI] [PubMed] [Google Scholar]
  18. Okudaira H., Sakurai Y., Terada K., Terada E., Ogita T., Miyamoto T. Cyclosporin A-induced suppression of ongoing IgE antibody formation in the mouse. Int Arch Allergy Appl Immunol. 1986;79(2):164–168. doi: 10.1159/000233965. [DOI] [PubMed] [Google Scholar]
  19. Peest D., Schaper B., Nashan B., Wonigeit K., Raude E., Pichlmayr R., Haverich A., Deicher H. High incidence of monoclonal immunoglobulins in patients after liver or heart transplantation. Transplantation. 1988 Sep;46(3):389–393. doi: 10.1097/00007890-198809000-00011. [DOI] [PubMed] [Google Scholar]
  20. Pritchard D. I. Immunity to helminths: is too much IgE parasite--rather than host-protective? Parasite Immunol. 1993 Jan;15(1):5–9. doi: 10.1111/j.1365-3024.1993.tb00566.x. [DOI] [PubMed] [Google Scholar]
  21. Prud'homme G. J., Parfrey N. A., Vanier L. E. Cyclosporine-induced autoimmunity and immune hyperreactivity. Autoimmunity. 1991;9(4):345–356. doi: 10.3109/08916939108997137. [DOI] [PubMed] [Google Scholar]
  22. Prud'homme G. J., Sanders R., Parfrey N. A., Ste-Croix H. T-cell maturation and clonal deletion in cyclosporine-induced autoimmunity. J Autoimmun. 1991 Apr;4(2):357–368. doi: 10.1016/0896-8411(91)90030-g. [DOI] [PubMed] [Google Scholar]
  23. Saxon A., Feldhaus J., Robins R. A. Single step separation of human T and B cells using AET treated srbc rosettes. J Immunol Methods. 1976;12(3-4):285–288. doi: 10.1016/0022-1759(76)90050-8. [DOI] [PubMed] [Google Scholar]
  24. Schreiber S. L., Crabtree G. R. The mechanism of action of cyclosporin A and FK506. Immunol Today. 1992 Apr;13(4):136–142. doi: 10.1016/0167-5699(92)90111-J. [DOI] [PubMed] [Google Scholar]
  25. Stellato C., de Paulis A., Ciccarelli A., Cirillo R., Patella V., Casolaro V., Marone G. Anti-inflammatory effect of cyclosporin A on human skin mast cells. J Invest Dermatol. 1992 May;98(5):800–804. doi: 10.1111/1523-1747.ep12499960. [DOI] [PubMed] [Google Scholar]
  26. Thomson A. W., Milton J. I., Aldridge R. D., Davidson R. J., Simpson J. G. Inhibition of drug-induced eosinophilia by cyclosporin A. Scand J Immunol. 1986 Aug;24(2):163–170. doi: 10.1111/j.1365-3083.1986.tb02082.x. [DOI] [PubMed] [Google Scholar]
  27. Thomson A. W., Moon D. K., Inoue Y., Geczy C. L., Nelson D. S. Modification of delayed-type hypersensitivity reactions to ovalbumin in cyclosporin A-treated guinea-pigs. Immunology. 1983 Feb;48(2):301–308. [PMC free article] [PubMed] [Google Scholar]
  28. Walz G., Zanker B., Melton L. B., Suthanthiran M., Strom T. B. Possible association of the immunosuppressive and B cell lymphoma-promoting properties of cyclosporine. Transplantation. 1990 Jan;49(1):191–194. doi: 10.1097/00007890-199001000-00042. [DOI] [PubMed] [Google Scholar]
  29. Wang J. M., Denis M., Fournier M., Laviolette M. Cyclosporin A increases the pulmonary eosinophilia induced by inhaled Aspergillus antigen in mice. Clin Exp Immunol. 1993 Sep;93(3):323–330. doi: 10.1111/j.1365-2249.1993.tb08180.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Webster L. M., Thomson A. W. Augmentation of delayed-type hypersensitivity to high dose sheep erythrocytes by cyclosporin A in the mouse: influence of drug dosage and route of administration and analysis of spleen cell populations. Clin Exp Immunol. 1988 Jan;71(1):149–154. [PMC free article] [PubMed] [Google Scholar]

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