Lack of effect of methimazole on thyrocyte cell-surface antigen expression.
The nature of the immunosuppressive effect of antithyroid drugs has been a subject of controversy. It has been claimed that these agents exert a direct effect on the immune system, although we and others have suggested that the drugs affect the thyroid cells primarily with consequent reduced thyrocyte-immunocyte signalling. This may occur from reduced thyroid hormone production and/or reduced antigen presentation by the thyrocytes to local T lymphocytes. Using a cytotoxicity assay system, with chromium-51 labelling, monoclonal antibodies against thyroperoxidase (TPO) and HLA-DR, and complement, we have measured the expression of TPO and HLA-DR on cultured normal human thyroid cells; we have also measured thyroglobulin (Tg) release by radioimmunoassay into the medium of the cultured cells. The thyroid cells were stimulated with TSH or thyrotropin binding inhibitory immunoglobulin (TBII) for 48 hours before measuring for TPO induction, and with interferon gamma (IFN-gamma) (with or without TSH or TBII) for thyrocyte HLA-DR expression. A dosage of 1.6 milliunits per ml of TSH resulted in a significant increase in TPO expression on thyrocytes when compared with control unstimulated thyroid cells (p less than 0.001). The concentrations of Tg released into the medium with TSH or TBII were also significantly higher than those of the control thyrocytes. IFN-gamma at 200 units per ml induced HLA-DR expression, but did not induce thyrocyte TPO expression, or Tg release. Addition of the antithyroid drug, methimazole (MMI), at different concentrations, in addition to the other stimulators, IFN-gamma, TSH, or TBII, did not result in any inhibition of TPO, Tg release, or HLA-DR expression on the thyroid cells. It would thus appear that the pathways for stimulation for the expression of TPO and HLA-DR appear to be different. Finally, MMI does not cause its immunosuppressive effect by any reduction of thyroid antigen expression or release.
Aguayo
J
J
Endocrinology Research Laboratory, Wellesley Hospital, University of Toronto, Canada.
Michaud
P
P
Iitaka
M
M
Degroot
L J
LJ
Row
V V
VV
Volpé
R
R
D000954:Antigens, Surface / Q000378:metabolism*; D001323:Autoantibodies / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating; D066298:In Vitro Techniques; D007453:Iodide Peroxidase / Q000276:immunology / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology*; D013954:Thyroglobulin / Q000378:metabolism; D013961:Thyroid Gland / Q000187:drug effects* / Q000276:immunology / Q000502:physiology; D013972:Thyrotropin / Q000494:pharmacology
D000954:Antigens, Surface; D001323:Autoantibodies; D006684:HLA-DR Antigens; D018828:Immunoglobulins, Thyroid-Stimulating; D008713:Methimazole; D013972:Thyrotropin; D013954:Thyroglobulin; D007453:Iodide Peroxidase