Inhibition of the receptor for interleukin-2 induced by carbimazole: relevance for the therapy of autoimmune thyroid disease.
Evidence has been accumulated that the anti-thyroid drugs used in the treatment of Graves' disease may have immunosuppressive properties but the exact mechanism of action is still unclear. In the present study, we have investigated the in vitro effect of carbimazole (CBZ) on the expression of lymphocyte differentiation antigens and on suppressor cell activity. The incorporation of radiolabelled methimazole (35S-MMI, the active metabolite of CBZ) by resting and mitogen stimulated lymphocytes was also investigated. CBZ at concentrations of 60 microM significantly inhibited the expression of the receptor for interleukin-2 (as defined by the anti-TAC monoclonal antibody [MoAb]) by lymphocytes stimulated with phytohaemagglutinin. The expression of an early activation antigen (as characterized by the 4F2 MoAb) was not affected. Twenty-four hour pre-incubation of cells with different concentrations of CBZ or medium alone did not change the lymphocyte response to mitogenic stimulation, thus suggesting no effect of the compound on suppressor cell function. Finally, there were no significant differences in the uptake of 35S-MMI between resting and stimulated lymphocytes. These data suggest that the immunosuppressive effect of CBZ may be due to its effect of reducing the expression of the receptor for interleukin-2 on lymphocytes undergoing full activation. This property of CBZ could be of relevance in the therapy of autoimmune thyroid diseases (not only Graves' disease) which are characterised by the presence of activated T cells in the thyroid and in circulation.
Signore
A
A
Pozzilli
P
P
Di Mario
U
U
Sensi
M
M
Beales
P
P
Andreani
D
D
D000328:Adult; D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface / Q000032:analysis; D001327:Autoimmune Diseases / Q000188:drug therapy; D002231:Carbimazole / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008713:Methimazole / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000187:drug effects*; D011971:Receptors, Immunologic / Q000187:drug effects*; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013959:Thyroid Diseases / Q000188:drug therapy
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D008713:Methimazole; D002231:Carbimazole