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The accumulation of [35S]methimazole by human and rat lymphocytes
Abstract:
The accumulation of 35S labelled methimazole (MMI) was examined in lymphocytes. No uptake of label was found in peripheral blood lymphocytes (PBL) from normal control subjects after in vitro incubation with the drug. Following administration of [35S]MMI to patients with Graves' hyperthyroidism PBL cell to plasma (C/P) 35S activity was greater than 1 in 4 of 11 patients and only in 1 of 7 other patients undergoing thyroidectomy. Thyroid lymphocytes from 2 of these patients showed some accumulation of activity. Following administration of [35S]MMI to normal rats C/P 35S ratios ranged from 1-5.6 but no 35S accumulation was found in PBL or thyroid lymphocytes from August strain rats in which experimental autoimmune thyroiditis had been produced. It is concluded that there is minimal, if any, significant accumulation of MMI in lymphocytes of patients with Graves' disease. The immunosuppressive action of MMI on lymphocyte antibody production must therefore by indirect.
Insights
Methimazole (MMI) does not accumulate significantly in lymphocytes of patients with Graves' disease. This suggests methimazole
Area of Science:
- Endocrinology
- Immunology
- Pharmacology
Background:
- Graves' disease is an autoimmune disorder affecting the thyroid.
- Methimazole (MMI) is a common antithyroid drug used to treat hyperthyroidism.
- The mechanism of MMI's immunosuppressive action on lymphocytes is not fully understood.
Purpose of the Study:
- To investigate the accumulation of radiolabeled methimazole (MMI) in lymphocytes.
- To determine if MMI directly affects lymphocyte function in Graves' disease patients.
Main Methods:
- In vitro incubation of peripheral blood lymphocytes (PBL) with [35S]MMI in normal subjects.
- Administration of [35S]MMI to Graves' hyperthyroidism patients and measurement of 35S activity in PBL and thyroid lymphocytes.
- Administration of [35S]MMI to normal rats and rats with experimental autoimmune thyroiditis.
Main Results:
- No [35S]MMI uptake was observed in PBL from normal controls in vitro.
- Elevated PBL to plasma 35S activity ratios were found in a subset of Graves' disease patients.
- Some 35S accumulation was detected in thyroid lymphocytes of two patients.
- No significant [35S]MMI accumulation was found in lymphocytes of rats, even those with experimental autoimmune thyroiditis.
Conclusions:
- Methimazole (MMI) shows minimal to no significant accumulation in lymphocytes of Graves' disease patients.
- The immunosuppressive effects of MMI on lymphocyte antibody production are likely indirect.
- Further research is needed to elucidate the indirect mechanisms of MMI's immunomodulatory actions.