Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1985 Aug;61(2):360–367.

Effect of in vitro colchicine and oral theophylline on suppressor cell function of asthmatic patients.

D Ilfeld, S Kivity, E Feierman, M Topilsky, O Kuperman
PMCID: PMC1577313  PMID: 2931223

Abstract

Extrinsic asthmatic patients have been reported to have a deficiency of concanavalin A (Con A)-induced suppressor cell function. We tested whether in vitro colchicine and oral theophylline can correct this immunoregulatory abnormality. Asthmatic patients' mononuclear cells were incubated with Con A and/or colchicine and then suppression of proliferation was measured by coculture of these cells with healthy volunteers' mononuclear cells and phytohaemagglutinin. The Con A induced suppressor cell function of 29 theophylline treated patients (26 +/- 16%, mean +/- s.d.) was significantly (P less than 0.002) increased as compared to 21 untreated patients (12 +/- 10%) but significantly (P less than 0.01) decreased as compared to 45 healthy volunteers (39 +/- 17%). A pharmacological concentration (10(-8) M) of colchicine had no significant effect on Con A-induced suppressor cell function of 19 untreated patients (from 12 +/- 9% to 9 +/- 22%) but significantly (P less than 0.05) increased Con A-induced suppressor cell function of 20 theophylline treated patients (from 26 +/- 17% to 36 +/- 19%). Thus asthmatic patients have decreased Con A-induced suppressor cell function which is partially corrected by oral theophylline and almost completely corrected by oral theophylline plus in vitro colchicine. This synergistic effect raises the possibility that oral colchicine together with theophylline may be useful in treating patients with extrinsic asthma.

Full text

PDF
360

Selected References

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

  1. Barakat M. H., El-Khawad A. O., Gumaa K. A., El-Sobki N. I., Fenech F. F. Metaraminol provocative test: a specific diagnostic test for familial Mediterranean fever. Lancet. 1984 Mar 24;1(8378):656–657. doi: 10.1016/s0140-6736(84)92172-x. [DOI] [PubMed] [Google Scholar]
  2. Canonica G. W., Mingari M. C., Melioli G., Colombatti M., Moretta L. Imbalances of T cell subpopulations in patients with atopic diseases and effect of specific immunotherapy. J Immunol. 1979 Dec;123(6):2669–2672. [PubMed] [Google Scholar]
  3. Dinarello C. A., Wolff S. M., Goldfinger S. E., Dale D. C., Alling D. W. Colchicine therapy for familial mediterranean fever. A double-blind trial. N Engl J Med. 1974 Oct 31;291(18):934–937. doi: 10.1056/NEJM197410312911804. [DOI] [PubMed] [Google Scholar]
  4. Engel P., Huguet J., Sanosa J., Sierra P., Cols N., García-Calderón P. A. T cell subsets in allergic respiratory disease using monoclonal antibodies. Ann Allergy. 1984 Oct;53(4):337–340. [PubMed] [Google Scholar]
  5. Fleisher T. A., Greene W. C., Blaese R. M., Waldmann T. A. Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. II. Characterization of a soluble suppressor of B cell immunoglobulin production. J Immunol. 1981 Mar;126(3):1192–1197. [PubMed] [Google Scholar]
  6. Gelfand E. W., Dosch H. M., Hastings B., Shore A. Lithium: a modulator of cyclic AMP-dependent events in lymphocytes? Science. 1979 Jan 26;203(4378):365–367. doi: 10.1126/science.216075. [DOI] [PubMed] [Google Scholar]
  7. Greene W. C., Fleisher T. A., Waldmann T. A. Soluble suppressor supernatants elaborated by concanavalin A-activated human mononuclear cells. I. Characterization of a soluble suppressor T cell proliferation. J Immunol. 1981 Mar;126(3):1185–1191. [PubMed] [Google Scholar]
  8. Greene W. C., Parker C. M., Parker C. W. Colchicine-sensitive structures and lymphocyte activation. J Immunol. 1976 Sep;117(3):1015–1022. [PubMed] [Google Scholar]
  9. Gupta S., Fikrig S., Good R. A. Subpopulations of human T lymphocytes. XIII. T cell subpopulations (T mu and T gamma) in children with bronchial asthma. Int Arch Allergy Appl Immunol. 1980;61(3):293–298. [PubMed] [Google Scholar]
  10. Halkin H., Dany S., Greenwald M., Shnaps Y., Tirosh M. Colchicine kinetics in patients with familial Mediterranean fever. Clin Pharmacol Ther. 1980 Jul;28(1):82–87. doi: 10.1038/clpt.1980.135. [DOI] [PubMed] [Google Scholar]
  11. Harper T. B., Gaumer H. R., Waring W., Brannon R. B., Salvaggio J. E. A comparison of cell-mediated immunity and suppressor T-cell function in asthmatic and normal children. Clin Allergy. 1980 Sep;10(5):555–563. doi: 10.1111/j.1365-2222.1980.tb02137.x. [DOI] [PubMed] [Google Scholar]
  12. Henderson W. R., Shelhamer J. H., Reingold D. B., Smith L. J., Evans R., 3rd, Kaliner M. Alpha-adrenergic hyper-responsiveness in asthma. N Engl J Med. 1979 Mar 22;300(12):642–647. doi: 10.1056/NEJM197903223001203. [DOI] [PubMed] [Google Scholar]
  13. Hsieh K. H. Changes of lymphoproliferative responses of T cell subsets to allergen and mitogen after hyposensitization in asthmatic children. J Allergy Clin Immunol. 1984 Jul;74(1):34–40. doi: 10.1016/0091-6749(84)90084-8. [DOI] [PubMed] [Google Scholar]
  14. Ilfeld D., Feierman E., Kuperman O., Kivity S., Topilsky M., Netzer L., Pecht M., Trainin N. Effect of colchicine on T cell subsets of healthy volunteers. Immunology. 1984 Nov;53(3):595–598. [PMC free article] [PubMed] [Google Scholar]
  15. Ilfeld D., Kuperman O. Correction of a suppressor cell deficiency in four patients with familial Mediterranean fever by in vitro or in vivo colchicine. Clin Exp Immunol. 1982 Oct;50(1):99–106. [PMC free article] [PubMed] [Google Scholar]
  16. Irons R. D., Pfeifer R. W., Aune T. M., Pierce C. W. Soluble immune response suppressor (SIRS) inhibits microtubule function in vivo and microtubule assembly in vitro. J Immunol. 1984 Oct;133(4):2032–2036. [PubMed] [Google Scholar]
  17. Kus J., Tse K. S., Enarson D., Grzybowski S., Chan-Yeung M. Lymphocyte subpopulations in patients with allergic rhinitis. Allergy. 1984 Oct;39(7):509–514. doi: 10.1111/j.1398-9995.1984.tb00871.x. [DOI] [PubMed] [Google Scholar]
  18. Logsdon P. J., Middleton E., Jr, Coffey R. G. Stimulation of leukocyte adenyl cyclase by hydrocortisone and isoproterenol in asthmatic and nonasthmatic subjects. J Allergy Clin Immunol. 1972 Jul;50(1):45–56. doi: 10.1016/0091-6749(72)90078-4. [DOI] [PubMed] [Google Scholar]
  19. Lomnitzer R., Phillips R., Rabson A. R. Suppression of interleukin-2 production by human concanavalin A-induced suppressor cells. Cell Immunol. 1984 Jul;86(2):362–370. doi: 10.1016/0008-8749(84)90391-5. [DOI] [PubMed] [Google Scholar]
  20. Malawista S. E., Oliver J. M., Rudolph S. A. Microtubules and cyclic AMP in human leukocytes: on the order of things. J Cell Biol. 1978 Jun;77(3):881–886. doi: 10.1083/jcb.77.3.881. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Nawata Y., Koike T., Yanagisawa T., Iwamoto I., Itaya T., Yoshida S., Tomioka H. Anti-IgE autoantibody in patients with bronchial asthma. Clin Exp Immunol. 1984 Nov;58(2):348–356. [PMC free article] [PubMed] [Google Scholar]
  22. Pardi R., Zocchi M. R., Ferrero E., Ciboddo G. F., Inverardi L., Rugarli C. In vivo effects of a single infusion of theophylline on human peripheral blood lymphocytes. Clin Exp Immunol. 1984 Sep;57(3):722–728. [PMC free article] [PubMed] [Google Scholar]
  23. Parker C. W., Smith J. W. Alterations in cyclic adenosine monophosphate metabolism in human bronchial asthma. I. Leukocyte responsiveness to -adrenergic agents. J Clin Invest. 1973 Jan;52(1):48–59. doi: 10.1172/JCI107173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rachelefsky G. S., Katz R. M., Siegel S. C. A sustained release theophylline preparation: efficacy in childhood asthma with low serum theophylline levels. Ann Allergy. 1978 Apr;40(4):252–257. [PubMed] [Google Scholar]
  25. Raupp L. C., Lum L. G., Oppenheim J. J., Blaese R. M., Olson D., Smith-Gill S. J. Enhanced cAMP production by activated human Fc-IgG receptor positive T-cell subpopulations. Clin Immunol Immunopathol. 1981 Oct;21(1):1–11. doi: 10.1016/0090-1229(81)90189-6. [DOI] [PubMed] [Google Scholar]
  26. Rivlin J., Kuperman O., Freier S., Godfrey S. Suppressor T-lymphocyte activity in wheezy children with and without treatment by hyposensitization. Clin Allergy. 1981 Jul;11(4):353–356. doi: 10.1111/j.1365-2222.1981.tb01605.x. [DOI] [PubMed] [Google Scholar]
  27. Rocklin R. E., Habarek-Davidson A. Pharmacologic modulation in vitro of human histamine-induced suppressor cell activity. Int J Immunopharmacol. 1984;6(3):179–186. doi: 10.1016/0192-0561(84)90015-8. [DOI] [PubMed] [Google Scholar]
  28. Rocklin R. E., Sheffer A. L., Greineder D. K., Melmon K. L. Generation of antigen-specific suppressor cells during allergy desensitization. N Engl J Med. 1980 May 29;302(22):1213–1219. doi: 10.1056/NEJM198005293022201. [DOI] [PubMed] [Google Scholar]
  29. Rola-Pleszczynski M., Blanchard R. Suppressor cell function in respiratory allergy. Modulation by aminophylline and isoproterenol. Int Arch Allergy Appl Immunol. 1981;64(4):361–370. doi: 10.1159/000232717. [DOI] [PubMed] [Google Scholar]
  30. Rudolph S. A., Greengard P., Malawista S. E. Effects of colchicine on cyclic AMP levels in human leukocytes. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3404–3408. doi: 10.1073/pnas.74.8.3404. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sakane T., Honda M., Taniguchi Y., Kotani H. Separation of concanavalin A-induced human suppressor and helper T cells by the autologous erythrocyte rosette technique. J Clin Invest. 1981 Aug;68(2):447–453. doi: 10.1172/JCI110274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schlesinger M., Ilfeld D., Handzel Z. T., Altman Y., Kuperman O., Levin S., Bibi C., Netzer L., Trainin N. Effect of colchicine on immunoregulatory abnormalities in familial Mediterranean fever. Clin Exp Immunol. 1983 Oct;54(1):73–79. [PMC free article] [PubMed] [Google Scholar]
  33. Shelhamer J. H., Metcalfe D. D., Smith L. J., Kaliner M. Abnormal beta adrenergic responsiveness in allergic subjects: analysis of isoproterenol-induced cardiovascular and plasma cyclic adenosine monophosphate responses. J Allergy Clin Immunol. 1980 Jul;66(1):52–60. doi: 10.1016/0091-6749(80)90138-4. [DOI] [PubMed] [Google Scholar]
  34. Shohat B., Volovitz B., Varsano I. Induction of suppressor T cells in asthmatic children by theophylline treatment. Clin Allergy. 1983 Sep;13(5):487–493. doi: 10.1111/j.1365-2222.1983.tb02626.x. [DOI] [PubMed] [Google Scholar]
  35. Spilberg I., Mandell B., Mehta J., Simchowitz L., Rosenberg D. Mechanism of action of colchicine in acute urate crystal-induced arthritis. J Clin Invest. 1979 Sep;64(3):775–780. doi: 10.1172/JCI109523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Strannegård O., Strannegård I. L. Effect of cyclic AMP-elevating agents on human spontaneous IgE synthesis in vitro. Int Arch Allergy Appl Immunol. 1984;74(1):9–14. doi: 10.1159/000233508. [DOI] [PubMed] [Google Scholar]
  37. Wolberg G., Stopford C. R., Zimmerman T. P. Antagonism by taxol of effects of microtubule-disrupting agents on lymphocyte cAMP metabolism and cell function. Proc Natl Acad Sci U S A. 1984 Jun;81(11):3496–3500. doi: 10.1073/pnas.81.11.3496. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES