Journal of Clinical Immunology

, Volume 2, Issue 4, pp 335–342 | Cite as

Effect of indomethacin on phytohemagglutinin-stimulated peripheral blood lymphocytes in thyroid autoimmune diseases

  • Furio Pacini
  • Philippe Fragu
  • Stefano Mariotti
  • Leslie J. DeGroot
Original Articles


Suppressor lymphocyte function was evaluated in control subjects and in patients with autoimmune thyroid disease, utilizing an assay in which indomethacin was added to lymphocyte cultures to inhibit prostaglandin-producing suppressor cells. This assay is based on the observation that the addition of indomethacin, a potent prostaglandin synthesis inhibitor, to phytohemagglutinin-stimulated peripheral blood lymphocytes should cause an increase in the incorporation of iododeoxyuridine in control subjects and a smaller increase in diseases with reduced prostaglandin-producing suppressor cells. The addition of indomethacin, 1 µg/ml, stimulated iododeoxyuridine incorporation in phytohemagglutinin-stimulated cultures in control subjects to an index value of 1.43 (i.e., the increment in iododeoxyuridine incorporation with both indomethacin and phytohemagglutinin was 43% greater than the incorporation with phytohemagglutinin alone). The stimulation index was significantly lower in patients with Graves' disease who were toxic and untreated (1.18±0.25, mean ± SD;P<0.003). Patients who were toxic while receiving antithyroid drugs or after radioiodine therapy or patients euthyroid after treatment had a mean stimulation index in the normal range, although the spread of data was very large in these groups. Responses in patients with Hashimoto's thyroiditis were also quite variable. The average response was 1.74±0.72, with 40% of the patients showing a high stimulation index. This study supports our previous investigations in which we used different assay systems for measuring suppressor-cell function in patients with thyroid autoimmune diseases and indicates that a defect in suppressor lymphocyte function is measurable by another technique. The abnormality persists in some cases after metabolic control has been achieved, but usually returns toward normal over months or years.

Key words

Indomethacin suppressor cells autoimmune thyroid disease 


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  1. 1.
    Kats DH, Benacerraf B: The regulatory influence of activated-T cells on B-cell responses to antigens. Adv Immunol 15:1–31, 1972Google Scholar
  2. 2.
    Gershon RK: A disquisition on suppressor T-cells. Transplant Rev 26:170–185, 1975Google Scholar
  3. 3.
    Waldmann TA, Broder S: Suppressor cells in the regulation of the immune response. Prog Clin Immunol 3:155–199, 1977Google Scholar
  4. 4.
    Saxon A, Stevens RH, Ashman RF: Regulation of immunoglobulin production in human peripheral blood leukocytes: Cellular interactions. J Immunol 118:1972–1979, 1977Google Scholar
  5. 5.
    Waldmann TA, Durm M, Broder S, Blease RM, Blackman M, Strober W: Role of suppressor T-cells in pathogenesis of common variable hypogammaglobulinemia. Lancet 2:609–613, 1974Google Scholar
  6. 6.
    Broom BC, DeLaConcha EG, Webster ADB, Janossy GJ, Asherson GL: Intracellular immunoglobulin production in vitro by lymphocytes from patients with hypogammaglobulinaemia and their effect on normal lymphocytes. Clin Exp Immunol 23:73–77, 1976Google Scholar
  7. 7.
    Kats SI, Parker D, Turk JL: B-cell suppression of delayed hypersensitivity reactions. Nature 251:550–551, 1974Google Scholar
  8. 8.
    Neta R, Salvin SB: T and B lymphocytes in the regulation of delayed hypersensitivity. J Immunol 117:2014–2020, 1976Google Scholar
  9. 9.
    Kirchner H, Fernbach BR, Herberman RB:In Mitogens in Immunobiology, JJ Oppenheimer, DL Rosenstreich (eds). Academic Press, New York, 1976, p 495Google Scholar
  10. 10.
    Stobo JD: Immunosuppression in man: Suppression by macrophages can be mediated by interactions with regulatory T-cells. J Immunol 119:918–924, 1977Google Scholar
  11. 11.
    Allison AC, Denman AM, Barnes RD: Cooperating and controlling functions of thymus-derived lymphocytes in relation to autoimmunity. Lancet 2:135–140, 1971Google Scholar
  12. 12.
    Waldmann TA, Blease RM, Broder S, Krakauer RS: Disorders of suppressor immunoregulatory cells in the pathogenesis of immunodeficiency and autoimmunity. Ann Intern Med 88:226–238, 1978Google Scholar
  13. 13.
    Shou L, Schwartz SA, Good RA: Suppressor cell activity after Concanavalin-A treatment of lymphocytes from normal donors. J Exp Med 143:1100–1110, 1976Google Scholar
  14. 14.
    Hubert C, Delespesse G, Govaerts A: Concanavalin-A activated suppressor cells in normal human peripheral blood lymphocytes. Clin Exp Immunol 26:95–98, 1976Google Scholar
  15. 15.
    Haynes BF, Fauci AS: Activation of human B lymphocytes, III. Concanavalin A induced generation of suppressor cells of the plaque-forming cell response of normal human B lymphocytes. J Immunol 118:2281–2287, 1977Google Scholar
  16. 16.
    Bresnihan B, Jasin HE: Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus. J Clin Invest 59:106–116, 1977Google Scholar
  17. 17.
    Okita N, Row VV, Volpe R: Suppressor T-lymphocytes deficiency in Graves' disease and Hashimoto's thyroiditis. J Clin Endocrinol Metab 52:528–533, 1981Google Scholar
  18. 18.
    Fauci AS, Steinberg AD, Haynes BF, Whaler G: Immunoregulatory aberrations in systemic lupus erythematosus. J Immunol 121:1473–1479, 1978Google Scholar
  19. 19.
    Sagawa A, Abdou NI: Suppressor cell dysfunction in systemic lupus erythematosus. Cells involved and in vitro correction. J Clin Invest 62:789–796, 1978Google Scholar
  20. 20.
    Morimoto C: Loss of suppressor T-lymphocyte function in patients with systemic lupus erythematosus (SLE). Clin Exp Immunol 32:125–133, 1978Google Scholar
  21. 21.
    Kaufman B, Bostwick E: Defective suppressor T-cell activity in systemic lupus erythematosus. Clin Immunol Immunopathol 13:9–18, 1979Google Scholar
  22. 22.
    Newman B, Blank S, Lomnitzer R, Disler P, Rabson AR: Lack of suppressor cell activity in systemic lupus erythematosus. Clin Immunol Immunopathol 13:187–193, 1979Google Scholar
  23. 23.
    Morimoto C, Abe T, Homma M: Altered function of suppressor T lymphocytes in patients with active lupus erythematosus. In vitro immune response to autoantigen. Clin Immunol Immunopathol 13:161–170, 1979Google Scholar
  24. 24.
    Hodgson HJF, Wands JR, Isselbacker KJ: Alteration in suppressor cell activity in chronic active hepatitis. Proc Natl Acad Sci (Wash) 75:1549–1553, 1978Google Scholar
  25. 25.
    Aoki N, Pinnamaneni KM, DeGroot LJ: Studies on suppressor cell function in thyroid diseases. J Clin Endocrinol Metab 48:803–810, 1979Google Scholar
  26. 26.
    Pacini F: Studies of T- and B-cell interactions in patients with Graves' disease. Ann Endocrinol 42:abstr 52, 1981Google Scholar
  27. 27.
    Goodwin JS, Bankhurst AD, Messner RP: Suppression of human T-cell mitogenesis by prostaglandin. J Exp Med 146: 1719–1734, 1977Google Scholar
  28. 28.
    Goodwin JS, Messner RP, Bankhurst AD, Peake GT, Saiki JH, Williams RC Jr: Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med 297:963–968, 1977Google Scholar
  29. 29.
    Goodwin JS, Dehoratious R, Israel H, Peake GT, Messner RP: Suppressor cell function in sarcoidosis. Ann Intern Med 90:169–173, 1979Google Scholar
  30. 30.
    Vosixa G, Thies J: Effect of indomethacin on blastogenesis of lymphocytes from cancer patients: Differentiation of patient types. Clin Immunol Immunopathol 13:30–38, 1979Google Scholar
  31. 31.
    Senhauser DA: Immune pathologic correlations in thyroid disease.In The Thyroid, JB Hazard, DE Smith (eds). Baltimore, Williams and Wilkins, 1974, pp 167–169Google Scholar
  32. 32.
    Amino N, Hagen SR, Yamada N, Refetoff S: Measurements of circulating thyroid microsomal antibodies by tanned red cell hemagglutination techniques: Its usefulness in the diagnosis of autoimmune thyroid diseases. Clin Endocrinol 5:115–125, 1976Google Scholar
  33. 33.
    Koski IR, Poplack DG, Blaese RM: A nonspecific esterase strain for the identification of monocytes and macrophages.In In Vitro Methods in Cell-Mediated and Tumor Immunity, BR Bloom, JR David (eds). New York, Academic Press, 1976, pp 359–362Google Scholar
  34. 34.
    Rice L, Laughter AH, Twomey JJ: Three suppressor systems in human blood that modulate lymphoproliferation. J Immunol 122:991–996, 1979Google Scholar
  35. 35.
    Goodwin JS, Messner RP, Peake GT: Prostaglandin suppression of mitogen-stimulated lymphocytes in vitro. Changes with the mitogen dose and preincubation. J Clin Invest 62:753–760, 1978Google Scholar
  36. 36.
    Mulaisho C, Abdou NI, Utiger RD: Lack of T-cell immune abnormalities in peripheral blood lymphocytes in patients with Graves' disease or hypothyroidism. J Clin Endocrinol Metab 41:266–270, 1975Google Scholar
  37. 37.
    DeGroot LJ, Jaksina S: Observations on the role of circulating lymphocytes in thyroid autoimmunity. J Clin Endocrinol Metab 29:207–212, 1969Google Scholar
  38. 38.
    Bonnyns M, Cano P, Osterland CK, McKenzie JM: Immune reactions in patients with Graves' disease. Am J Med 65:971–977, 1978Google Scholar
  39. 39.
    Balazs C, Leovey A, Bordan L: Decrease of concanavalin A activated and short lived suppressor T cell function in thyrotoxicosis. Biomedicine 30:143–147, 1979Google Scholar
  40. 40.
    Greaves M, Janossy G: Elicitation of selective T and B lymphocyte responses by cell surface binding ligands. Transplant Rev 11:87–130, 1972Google Scholar

Copyright information

© Plenum Publishing Corporation 1982

Authors and Affiliations

  • Furio Pacini
    • 1
  • Philippe Fragu
    • 1
  • Stefano Mariotti
    • 1
  • Leslie J. DeGroot
    • 1
  1. 1.The Thyroid Study Unit, Department of MedicineThe University of ChicagoChicago

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