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British Medical Journal (Clinical Research Ed.) logoLink to British Medical Journal (Clinical Research Ed.)
. 1984 Feb 18;288(6416):518–520. doi: 10.1136/bmj.288.6416.518

Methimazole and generation of oxygen radicals by monocytes: potential role in immunosuppression.

A P Weetman, M E Holt, A K Campbell, R Hall, A M McGregor
PMCID: PMC1444568  PMID: 6421361

Abstract

A study was conducted investigating the possibility that the immunosuppressive action of methimazole (the active metabolite of the antithyroid drug carbimazole) might be due to an effect on the production of oxygen radicals by monocytes. Techniques comprised measurement of luminol dependent chemoluminescence in monocytes and a spectrophotometric assay for production of hydrogen peroxide. The results showed definite inhibition of formation of oxygen radicals by resting and stimulated monocytes, which may explain the immunosuppressive action of the drug in Graves' disease. The findings also suggest that the formation of oxygen radicals and the initiation of the immune response may be closely related.

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Selected References

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

  1. Babior B. M. Oxygen-dependent microbial killing by phagocytes (first of two parts). N Engl J Med. 1978 Mar 23;298(12):659–668. doi: 10.1056/NEJM197803232981205. [DOI] [PubMed] [Google Scholar]
  2. Cohen G., Heikkila R. E., Allis B., Cabbat F., Dembiec D., MacNamee D., Mytilineou C., Winston B. Destruction of sympathetic nerve terminals by 6-hydroxydopamine: protection by 1-phenyl-3-(2-thiazolyl)-2-thiourea, diethyldithiocarbamate, methimazole, cysteamine, ethanol and n-butanol. J Pharmacol Exp Ther. 1976 Nov;199(2):336–352. [PubMed] [Google Scholar]
  3. Connell J. M., McCruden D. C., Small M., Ferguson M. M., Alexander W. D. Accumulation of thiourylene antithyroid drugs in mouse salivary gland. J Endocrinol. 1983 Jan;96(1):91–96. doi: 10.1677/joe.0.0960091. [DOI] [PubMed] [Google Scholar]
  4. Easmon C. S., Cole P. J., Williams A. J., Hastings M. The measurement of opsonic and phagocytic function by Luminol-dependent chemiluminescence. Immunology. 1980 Sep;41(1):67–74. [PMC free article] [PubMed] [Google Scholar]
  5. Engler H., Taurog A., Luthy C., Dorris M. L. Reversible and irreversible inhibition of thyroid peroxidase-catalyzed iodination by thioureylene drugs. Endocrinology. 1983 Jan;112(1):86–95. doi: 10.1210/endo-112-1-86. [DOI] [PubMed] [Google Scholar]
  6. Fantone J. C., Ward P. A. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions. Am J Pathol. 1982 Jun;107(3):395–418. [PMC free article] [PubMed] [Google Scholar]
  7. Lam D. C., Lindsay R. H. Accumulation of 2-[14C]propylthiouracil in human polymorphonuclear leukocytes. Biochem Pharmacol. 1979 Aug 1;28(15):2289–2296. doi: 10.1016/0006-2952(79)90692-0. [DOI] [PubMed] [Google Scholar]
  8. McGregor A. M., Petersen M. M., McLachlan S. M., Rooke P., Smith B. R., Hall R. Carbimazole and the autoimmune response in Graves' disease. N Engl J Med. 1980 Aug 7;303(6):302–307. doi: 10.1056/NEJM198008073030603. [DOI] [PubMed] [Google Scholar]
  9. Nathan C. F. Secretion of oxygen intermediates: role in effector functions of activated macrophages. Fed Proc. 1982 Apr;41(6):2206–2211. [PubMed] [Google Scholar]
  10. Pick E., Mizel D. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods. 1981;46(2):211–226. doi: 10.1016/0022-1759(81)90138-1. [DOI] [PubMed] [Google Scholar]
  11. Rosen H., Klebanoff S. J. Chemiluminescence and superoxide production by myeloperoxidase-deficient leukocytes. J Clin Invest. 1976 Jul;58(1):50–60. doi: 10.1172/JCI108458. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Segal A. W., Jones O. T. The subcellular distribution and some properties of the cytochrome b component of the microbicidal oxidase system of human neutrophils. Biochem J. 1979 Jul 15;182(1):181–188. doi: 10.1042/bj1820181. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Shewring G. S., Lazarus J. H. The accumulation of [35S]methimazole by human and rat lymphocytes. Acta Endocrinol (Copenh) 1983 Jan;102(1):68–70. doi: 10.1530/acta.0.1020068. [DOI] [PubMed] [Google Scholar]
  14. Weetman A. P., McGregor A. M., Hall R. Methimazole inhibits thyroid autoantibody production by an action on accessory cells. Clin Immunol Immunopathol. 1983 Jul;28(1):39–45. doi: 10.1016/0090-1229(83)90186-1. [DOI] [PubMed] [Google Scholar]

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