The absence of any effect of methimazole on in vitro cell-mediated cytotoxicity

Two recent studies have reported that antithyroid drugs inhibit killer (K) and natural killer (NK) cell function in vitro, which could be relevant to the changes in these cell populations during treatment of Graves' disease. In contrast to these reports we have found no in vitro effect of pharmacologically relevant concentrations of methimazole (MMI) (100 mumol/l) on (i) NK cell function using K562 cells or MOLT-4 cells as targets, (ii) K cell function using antibody-dependent cytotoxicity assays with L929 cells or thyroid-antigen-coated chick red cells, or (iii) monocyte-dependent cytotoxin-mediated killing of L929 cells. Enhanced cytotoxicity was found with 1 mmol/l MMI in some of these assays but this was not consistent since it occurred only in certain individual cultures. Since we have shown previously that 100 mumol/l MMI inhibits oxygen radical generation, the present results add to the evidence that these radicals are not directly involved in cell-mediated cytotoxicity and do not support the concept that antithyroid drugs have a significant effect on antibody-dependent cell-mediated cytotoxicity in Graves' disease.