METABOLISM OF GLUCOSE AND GLUTAMINE IN LYMPHOCYTES FROM GRAVES HYPERTHYROID PATIENTS - INFLUENCE OF METHIMAZOLE TREATMENT

Several studies have shown that thyroid hormones are able to influence selected immune responses such as cell mediated immunity, differentia tion of B lymphocytes and the activity of NK cells. These hormones can also regulate the metabolism of glucose and glutamine in rat macropha ges and their effects seem to occur mainly through the Krebs cycle. Al terations in the hexokinase, citrate synthase, glucose-6-phosphate deh ydrogenase and glutaminase activities in lymphocytes from patients wit h Graves' disease, either untreated or on methimazole (MMI) therapy we re investigated. Experiments were also done in vitro to determine the activities of these enzymes in normal lymphocytes cultured for 24h in the presence of MMI, T-3 and T-4 using concentrations close to the phy siological. Changes in the conversion of [U-C-14]-glucose and [U-C-14] -glutamine to (CO2)-C-14 as caused by the addition of MMI, T-3 or T-4 to the culture medium were also evaluated. The results indicate that h igh levels of thyroid hormones might stimulate the metabolism of gluco se and glutamine for a short period of time but, if the stimulus is ma intained, the utilization of glutamine by lymphocytes is then suppress ed. Moreover, MMI does affect lymphocyte metabolism but the significan ce of this finding for its immunosuppressive effect remains to be exam ined.