Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1972 Sep;51(9):2233–2238. doi: 10.1172/JCI107031

The effect of azathioprine on gammaglobulin synthesis in man

Joshua Levy 1,2,3, Eugene V Barnett 1,2,3, Norman S MacDonald 1,2,3, James R Klinenberg 1,2,3, Carl M Pearson 1,2,3
PMCID: PMC292386  PMID: 4629438

Abstract

The effect of azathioprine therapy on gammaglobulin synthesis was evaluated in nine patients with rheumatic disorders. The rates of synthesis of IgG and IgM were calculated before and after 4 months of azathioprine treatment using turnover studies of radioiodinated gammaglobulins.

The synthesis of IgG decreased 33.4% of the initial IgG synthetic rate. Seven of nine patients showed reductions of IgG synthesis ranging from 16.8 to 74.1%. IgM production decreased from 24.5 to 74.2% in eight of nine patients with a mean reduction of 40.9%. Studies before and after a control period of 4 months of placebo in six patients revealed a mean increase in IgG and IgM synthesis. Serum immunoglobulin concentrations after 4 months of azathioprine treatment were not consistently reduced and did not parallel changes in immunoglobulin synthesis.

Reduced gammaglobulin synthesis may play a role in the therapeutic action of this and other “immunosuppressive” drugs.

Full text

PDF
2233

Images in this article

Selected References

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

  1. 1958 REVISION of diagnostic criteria for rheumatoid arthritis. Arthritis Rheum. 1959 Feb;2(1):16–20. doi: 10.1002/1529-0131(195902)2:1<16::aid-art1780020104>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  2. BARNETT E. V., BAKEMEIER R. F., LEDDY J. P., VAUGHAN J. H. HETEROGENEITY OF ANTINUCLEAR FACTORS IN LUPUS ERYTHEMATOSUS AND RHEUMATOID ARTHRITIS. Proc Soc Exp Biol Med. 1965 Mar;118:803–806. doi: 10.3181/00379727-118-29976. [DOI] [PubMed] [Google Scholar]
  3. BARNETT E. V., CONDEMI J. J., LEDDY J. P., VAUGHAN J. H. GAMMA-2, GAMMA-1A AND GAMMA-1M ANTINUCLEAR FACTORS IN HUMAN SERA. J Clin Invest. 1964 Jun;43:1104–1115. doi: 10.1172/JCI104995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BERSON S. A., YALOW R. S., SCHREIBER S. S., POST J. Tracer experiments with I131 labeled human serum albumin: distribution and degradation studies. J Clin Invest. 1953 Aug;32(8):746–768. doi: 10.1172/JCI102789. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Bach J. F., Dardenne M., Fournier C. In vitro evaluation of immunosuppressive drugs. Nature. 1969 Jun 7;222(5197):998–999. doi: 10.1038/222998a0. [DOI] [PubMed] [Google Scholar]
  7. Brocteur J., Moens C. Treatment of rheumatoid arthritis with immunosuppressive drugs. II. Immunological study. Acta Rheumatol Scand. 1965;11(3):221–230. doi: 10.3109/rhe1.1965.11.issue-1-4.26. [DOI] [PubMed] [Google Scholar]
  8. FAHEY J. L., ROBINSON A. G. FACTORS CONTROLLING SERUM GAMMA-GLOBULIN CONCENTRATION. J Exp Med. 1963 Nov 1;118:845–868. doi: 10.1084/jem.118.5.845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Herrod H. G., Myers M., Self K. S., Cooper M. D. Suppression of IgM and IgG synthesis in young rabbits by 6-methyl mercaptopurine treatment. J Lab Clin Med. 1970 Jul;76(1):1–9. [PubMed] [Google Scholar]
  10. Hurd E. R., Ziff M. Studies on the anti-inflammatory action of 6-mercaptopurine. J Exp Med. 1968 Oct 1;128(4):785–800. doi: 10.1084/jem.128.4.785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. KIRKPATRICK C. H., WILSON W. E., TALMAGE D. W. IMMUNOLOGIC STUDIES IN HUMAN ORGAN TRANSPLANTATION. I. OBSERVATION AND CHARACTERIZATION OF SUPPRESSED CUTANEOUS REACTIVITY IN UREMIA. J Exp Med. 1964 May 1;119:727–742. doi: 10.1084/jem.119.5.727. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KUNKEL H. G., TAN E. M. AUTOANTIBODIES AND DISEASE. Adv Immunol. 1964;27:351–395. doi: 10.1016/s0065-2776(08)60711-7. [DOI] [PubMed] [Google Scholar]
  13. LAPLANTE E. S., CONDIE R. M., GOOD R. A. Prevention of secondary immune response with 6-mercaptopurine. J Lab Clin Med. 1962 Apr;59:542–549. [PubMed] [Google Scholar]
  14. LEVIN R. H., LANDY M., FREI E., 3rd THE EFFECT OF 6-MERCAPTOPURINE ON IMMUNE RESPONSE IN MAN. N Engl J Med. 1964 Jul 2;271:16–22. doi: 10.1056/NEJM196407022710103. [DOI] [PubMed] [Google Scholar]
  15. Levy J., Barnett E. V., MacDonald N. S., Klinenberg J. R. Altered immunoglobulin metabolism in systemic lupus erythematosus and heumatoid arthritis. J Clin Invest. 1970 Apr;49(4):708–715. doi: 10.1172/JCI106283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. MAIBACH H. I., EPSTEIN W. L. IMMUNOLOGIC RESPONSES OF HEALTHY VOLUNTEERS RECEIVING AZATHIOPRINE (IMURAN). Int Arch Allergy Appl Immunol. 1965;27:102–109. doi: 10.1159/000229603. [DOI] [PubMed] [Google Scholar]
  17. MELLORS R. C., NOWOSLAWSKI A., KORNGOLD L., SENGSON B. L. Rheumatoid factor and the pathogenesis of rheumatoid arthritis. J Exp Med. 1961 Feb 1;113:475–484. doi: 10.1084/jem.113.2.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. McFARLANE A. S. The behavior of I 131-labeled plasma proteins in vivo. Ann N Y Acad Sci. 1957 Aug 30;70(1):19–25. doi: 10.1111/j.1749-6632.1957.tb35374.x. [DOI] [PubMed] [Google Scholar]
  19. Mistilis S. P., Blackburn C. R. The treatment of active chronic hepatitis with 6-mercaptopurine and azathioprine. Australas Ann Med. 1967 Nov;16(4):305–311. doi: 10.1111/imj.1967.16.4.305. [DOI] [PubMed] [Google Scholar]
  20. Mott P. D., Wochner R. D., Wolff S. M. The effect of 6-mercaptopurine on the turnover of I-131-gamma globulin and I125-albumin in rabbits. J Pharmacol Exp Ther. 1968 Jan;159(1):211–215. [PubMed] [Google Scholar]
  21. OLHAGEN B., BIRKE G., PLANTIN L. O., AHLINDER S. ISOTOPE STUDIES OF GAMMAGLOBULIN CATABOLISM IN COLLAGEN DISORDERS. Acta Rheumatol Scand. 1963;9:88–93. doi: 10.3109/rhe1.1963.9.issue-1-4.13. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. PLOTZ C. M., SINGER J. M. The latex fixation test. I. Application to the serologic diagnosis of rheumatoid arthritis. Am J Med. 1956 Dec;21(6):888–892. [PubMed] [Google Scholar]
  24. RUBIN A. L., STENZEL K. H., HIRSCHHORN K., BACH F. HISTOCOMPATIBILITY AND IMMUNOLOGIC COMPETENCE IN RENAL HOMOTRANSPLANTATION. Science. 1964 Feb 21;143(3608):815–816. doi: 10.1126/science.143.3608.815. [DOI] [PubMed] [Google Scholar]
  25. SCHWARTZ R., STACK J., DAMESHEK W. Effect of 6-mercaptopurine on antibody production. Proc Soc Exp Biol Med. 1958 Oct;99(1):164–167. doi: 10.3181/00379727-99-24281. [DOI] [PubMed] [Google Scholar]
  26. SELL S. EVIDENCE FOR SPECIES' DIFFERENCES IN THE EFFECT OF SERUM GAMMA-GLOBULIN CONCENTRATION ON GAMMA-GLOBULIN CATABOLISM. J Exp Med. 1964 Nov 1;120:967–986. doi: 10.1084/jem.120.5.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. SELL S., FAHEY J. L. RELATIONSHIP BETWEEN GAMMA-GLOBULIN METABOLISM AND LOW SERUM GAMMA-GLOBULIN IN GERMFREE MICE. J Immunol. 1964 Jul;93:81–87. [PubMed] [Google Scholar]
  28. SOLOMON A., WALDMANN T. A., FAHEY J. L. Clinical and experimental metabolism of normal 6.6s gamma-globulin in normal subjects and in patients with macroglobulinemia and multiple myeloma. J Lab Clin Med. 1963 Jul;62:1–17. [PubMed] [Google Scholar]
  29. STERLING K. The turnover rate of serum albumin in man as measured by I131-tagged albumin. J Clin Invest. 1951 Nov;30(11):1228–1237. doi: 10.1172/JCI102542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Swanson M. A., Schwartz R. S. Immunosuppressive therapy. The relation between clinical response and immunologic competence. N Engl J Med. 1967 Jul 27;277(4):163–170. doi: 10.1056/NEJM196707272770401. [DOI] [PubMed] [Google Scholar]
  31. Terasaki P. I., Mottironi V. D., Barnett E. V. Cytotoxins in disease. Autocytotoxins in lupus. N Engl J Med. 1970 Oct 1;283(14):724–728. doi: 10.1056/NEJM197010012831403. [DOI] [PubMed] [Google Scholar]
  32. Tesar J. T., Schmid F. R. Conversion of soluble immune complexes into complement-fixing aggregates by IgM-rheumatoid factor. J Immunol. 1970 Nov;105(5):1206–1214. [PubMed] [Google Scholar]
  33. WALDMANN T. A., SCHWAB P. J. IGG (7 S GAMMA GLOBULIN) METABOLISM IN HYPOGAMMAGLOBULINEMIA: STUDIES IN PATIENTS WITH DEFECTIVE GAMMA GLOBULIN SYNTHESIS, GASTROINTESTINAL PROTEIN LOSS, OR BOTH. J Clin Invest. 1965 Sep;44:1523–1533. doi: 10.1172/JCI105259. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. WOLFF S. M., GOODMAN H. C. Effect of purine antimetabolites on serum globulins in the rabbit. Proc Soc Exp Biol Med. 1963 Feb;112:416–419. doi: 10.3181/00379727-112-28062. [DOI] [PubMed] [Google Scholar]
  35. Wochner R. D. Hypercatabolism of normal IgG; an unexplained immunoglobulin abnormality in the connective tissue diseases. J Clin Invest. 1970 Mar;49(3):454–464. doi: 10.1172/JCI106254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Zvaifler N. J., Schur P. Reactions of aggregated mercaptoethanol treated gamma globulin with rheumatoid factor--precipitin and complement fixation studies. Arthritis Rheum. 1968 Aug;11(4):523–536. doi: 10.1002/art.1780110402. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES