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. 1988 Nov;74(2):258–263.

Immunomodulation by methimazole therapy in Graves' disease: rapid changes in activation stage of circulating regulatory T cell subsets, B cells and NK cells.

F A Karlsson 1, T H Tötterman 1
PMCID: PMC1541796  PMID: 2906281

Abstract

In patients with Graves' disease, initiation of thyrostatic therapy with methimazole causes a selective reduction of thyroid but not other autoantibody levels. The mechanism of this immunosuppressive effect is unknown. In the present study, methimazole (20 mg daily) induced very rapid changes in the surface antigen expression of several circulating lymphocyte subpopulations in six patients with Graves' disease. Within 1 to 3 days of therapy, the proportions of HLA-DR+ cells within the CD8+(Leu 2+) subset (activated 'suppressor/cytotoxic' T cells), CD11+(Leu 15+) cells out of CD8+ cells ('suppressor' T cells), and CD45+R (Leu 18+) cells out of CD4+(LEU 3+) cells ('suppressor/inducer' T cells) increased significantly from 4.7 +/- 3.9% to 9.5 +/- 6.0%, from 7.5 +/- 1.5% to 17 +/- 5.8% and from 49 +/- 17% to 73 +/- 19%, respectively. In parallel, the percentages of DR+ cells within the CD4+(Leu 3+) subset (activated 'helper' T cells), 4F2+ cells out of CD19+(Leu 12+) cells (activated B cells) and 4F2+ cells out of CD16+(Leu 11+) cells (activated 'natural killer'-like cells) declined significantly from 7.2 +/- 5.6% to 2.8 +/- 2.1%, from 7.2 +/- 1.5% to 4.0 +/- 2.8% and from 5.5 +/- 3.5% to 2.8 +/- 4.9% at 3 days, respectively. In contrast, no consistent phenotypic changes occurred in lymphocytes drawn from six healthy subjects during 7 days of methimazole medication. Direct in vitro effects of methimazole on lymphocyte markers were not observed when blood mononuclear cells from untreated patients were incubated with either the drug (10(-4) and 10(-6)M) or with autologous pre/post treatment serum for 1 to 4 days. Methimazole thus induces rapid alterations in the subclass and activation marker expression of circulating lymphocyte populations in Graves' disease. These alterations are compatible with a down-regulation of B cell activity. Indirect evidence suggests that the thyroid gland is the source of secondary signals for these changes to take place.

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Selected References

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

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