Production of and response to interleukin-2 in Graves' disease

Interleukin-2 is a lymphokine which is believed to play a central role in the regulation of the immune response. The production of and response to interleukin-2 were determined in hyperthyroid Graves' patients together with thyroid function and serum thyrotropin receptor antibody, a marker of autoimmune activity. Interleukin-2 production by mitogen-induced peripheral blood mononuclears was markedly low in 24 of 29 patients when compared to controls. Five patients in remission had normal values. In nine patients followed during antithyroid drug therapy, interleukin-2 production returned gradually to normal levels within 4–6 months. This rise and the concomitant decrease in serum thyrotropin receptor antibody correlated with the decline in the free thyroxin index. Antithyroid drugs and triiodothyronine had no effect on interleukin-2 productionin vitro. Mitogen-activated mononuclears from hyperthyroid Graves' patients did not proliferate as well as the controls in response to interleukin-2. However, seven patients treated with antithyroid drugs and three in remission responded normally. Flow cytometry using anti-Tac antibody revealed that the interleukin-2 receptor density on mononuclears from five patients was low. This parameter was normal in treated patients and those in remission. We conclude that the production of and response to interleukin-2 by peripheral blood mononuclears from hyperthyroid Graves' patients are poor, the latter being due to impaired receptor expression. Both aberrations are restored to normal by antithyroid drug therapy or in remission. The relative roles of the autoimmune process and thyroid function in modulating the interleukin-2 pathway and the question of whether antithyroid drugs act directly or through thyroid inhibition remain to be clarified.