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EFFECT OF THE ANTI‐THYROID DRUG METHIMAZOLE ON INTERLEUKIN‐1 AND INTERLEUKIN‐2 LEVELS IN VITRO

There is now good evidence that anti‐thyroid drugs such as methimazole have immunomodulatory effects which may be important in the treatment of patients with Graves' disease, but the immunological mechanisms by which these agents act are not clear. This study has examined the effect of methimazole on four important soluble mediators of the immune response, interleukin‐1 (IL‐1), interleukin‐2 (IL‐2), γ‐interferon (γ‐IFN) and B‐cell differentiation factor (BCDF). When peripheral blood mononuclear cells from normal subjects were stimulated with mitogens (phytohaemagglutinin, concanavalin A or pokeweed mitogen) in the presence of 10–100 μmol/l methimazole, there was an increase in IL‐2 activity in the culture supernatants. This effect was apparent between 24 and 60 h: enhanced proliferation of T‐cells was also seen in methimazole‐supplemented cultures. There was no effect of the drug on IL‐2 receptor expression or on IL‐1 and γ‐IFN production. BCDF was increased by methimazole in one of three experiments with pokeweed mitogen but not in three experiments with concanavalin A. These results suggest that the enhancement of mitogen‐stimulated T‐cell proliferation in vitro with methimazole is due to an increase in the IL‐2 available to the T‐cells in these cultures. Thus the in‐vivo immunological effects of these drugs are likely to be complex since they may have at least two, possibly related, actions on the intrathyroidal lymphoid infiltrate, namely inhibiting oxygen radical generation and increasing IL‐2 levels.