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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1976 Nov;26(2):346–354.

Comparative study of cyclophosphamide, 6-mercaptopurine, azathiopurine and methotrexate. Relative effects on the humoral and the cellular immune response in the mouse.

I G Otterness, Y H Chang
PMCID: PMC1540853  PMID: 991462

Abstract

The effects of cyclophosphamide, methotrexate, azathioprine and 6-mercaptopurine on the concomitant development of the humoral and the cellular immune responses of mice to a single antigen, the El4 tumour cell, were investigated. The measurements of cellular and humoral immunity were carried out in the same animal using lymphocyte and antibody mediated lysis of the El4 cell, a measurement system independent of underlying anti-inflammatory effects. A regimen of daily cyclophosphamide had a more pronounced suppressive effect on the humoral response than on the cellular response, in agreement with other investigators. A single low dose of cyclophosphamide stimulated the cellular response and suppressed the humoral response. Single or multiple high doses of cyclophosphamide maximally suppressed both the cellular and humoral response. Azathioprine and 6-mercaptopurine, in contrast to the results of other investigations, caused equivalent inhibition of both the humoral and cellular responses and thus lacked selectivity. Methotrexate also provided equivalent inhibition of both the humoral and cellular responses at all dose levels investigated.

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Selected References

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

  1. Abdou N. I., Zweiman B., Casella S. R. Effects of azathioprine therapy on bone marrow-dependent and thymus-dependent cells in man. Clin Exp Immunol. 1973 Jan;13(1):55–64. [PMC free article] [PubMed] [Google Scholar]
  2. Askenase P. W., Hayden B. J., Gershon R. K. Augmentation of delayed-type hypersensitivity by doses of cyclophosphamide which do not affect antibody responses. J Exp Med. 1975 Mar 1;141(3):697–702. doi: 10.1084/jem.141.3.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BOREL Y., SCHWARTZ R. INHIBITION OF IMMEDIATE AND DELAYED HYPERSENSITIVITY IN THE RABBIT BY 6-MERCAPTOPURINE. J Immunol. 1964 May;92:754–761. [PubMed] [Google Scholar]
  4. Camiener G. W., Wechter W. J. Immunosuppression--agents, procedures, speculations and prognosis. Prog Drug Res. 1972;16:67–156. doi: 10.1007/978-3-0348-7081-8_2. [DOI] [PubMed] [Google Scholar]
  5. Campbell A. C., Skinner J. M., Hersey P., Roberts-Thomson P., MacLennan I. C., Truelove S. C. Immunosuppression in the treatment of inflammatory bowel disease. I. Changes in lymphoid sub-populations in the blood and rectal mucosa following cessation of treatment with azathioprine. Clin Exp Immunol. 1974 Apr;16(4):521–533. [PMC free article] [PubMed] [Google Scholar]
  6. Canty T. G., Wunderlich J. R. Quantitative in vitro assay of cytotoxic cellular immunity. J Natl Cancer Inst. 1970 Oct;45(4):761–772. [PubMed] [Google Scholar]
  7. Dukor P., Dietrich F. M. The immune response to heterologous red cells in mice. V. The effect of cyclophosphamide and cortisone on antigenic competition. J Immunol. 1970 Jul;105(1):118–125. [PubMed] [Google Scholar]
  8. Galanaud P., Crevon M. C., Dormont J. Effect of azathioprine on in vitro antibody response. Differential effect on B cells involved in thymus-dependent and independent responses. Clin Exp Immunol. 1975 Oct;22(1):139–152. [PMC free article] [PubMed] [Google Scholar]
  9. Gorczynski R. M. Immunity to murine sarcoma virus-inducted tumors. II. Suppression of T cell-mediated immunity by cells from progressor animals. J Immunol. 1974 May;112(5):1826–1838. [PubMed] [Google Scholar]
  10. Katz S. I., Parker D., Turk J. L. B-cell suppression of delayed hypersensitivity reactions. Nature. 1974 Oct 11;251(5475):550–551. doi: 10.1038/251550a0. [DOI] [PubMed] [Google Scholar]
  11. Kerckhaert J. A., Van den Berg G. J., Willers J. M. Influence of cyclophosphamide on the delayed hypersensitivity of the mouse. Ann Immunol (Paris) 1974 Mar-Apr;125(3):415–426. [PubMed] [Google Scholar]
  12. Lagrange P. H., Mackaness G. B., Miller T. E. Influence of dose and route of antigen injection on the immunological induction of T cells. J Exp Med. 1974 Mar 1;139(3):528–542. doi: 10.1084/jem.139.3.528. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lerman S. P., Weidanz W. P. The effect of cyclophosphamide on the ontogeny of the humoral immune response in chickens. J Immunol. 1970 Sep;105(3):614–619. [PubMed] [Google Scholar]
  14. Mackaness G. B., Lagrange P. H., Miller T. E., Ishibashi T. Feedback inhibition of specifically sensitized lymphocytes. J Exp Med. 1974 Mar 1;139(3):543–559. doi: 10.1084/jem.139.3.543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. PAGE A. R., CONDIE R. M., GOOD R. A. Effect of 6-mercaptopurine on inflammation. Am J Pathol. 1962 May;40:519–530. [PMC free article] [PubMed] [Google Scholar]
  16. Röllinghoff M., Schrader J., Wagner H. Effect of azathioprine and cytosine arabinoside on humoral and cellular immunity in vitro. Clin Exp Immunol. 1973 Oct;15(2):261–269. [PMC free article] [PubMed] [Google Scholar]
  17. SANDERSON A. R. APPLICATIONS OF ISO-IMMUNE CYTOLYSIS USING RADIOLABELLED TARGET CELLS. Nature. 1964 Oct 17;204:250–253. doi: 10.1038/204250a0. [DOI] [PubMed] [Google Scholar]
  18. Santos G. W. Symposium on immunosuppressive drugs. Immunosuppressive drugs. I. Fed Proc. 1967 May-Jun;26(3):907–913. [PubMed] [Google Scholar]
  19. Turk J. L., Poulter L. W. Selective depletion of lymphoid tissue by cyclophosphamide. Clin Exp Immunol. 1972 Feb;10(2):285–296. [PMC free article] [PubMed] [Google Scholar]
  20. Winkelstein A. Differential effects of immunosuppressants on lymphocyte function. J Clin Invest. 1973 Sep;52(9):2293–2299. doi: 10.1172/JCI107417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Zweiman B., Phillips S. M. In vitro lymphocyte reactivity during depression of tuberculin hypersensitivity by 6-mercaptopurine. Science. 1970 Jul 17;169(3942):284–285. doi: 10.1126/science.169.3942.284. [DOI] [PubMed] [Google Scholar]

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