DIFFERENT CYTOKINE MESSENGER-RNA PROFILES IN GRAVES-DISEASE, HASHIMOTOS-THYROIDITIS, AND NONAUTOIMMUNE THYROID-DISORDERS DETERMINED BY QUANTITATIVE REVERSE-TRANSCRIPTASE POLYMERASE CHAIN-REACTION (RT-PCR)

Intrathyroidal lymphocytes are a source of cytokines thought to stimul ate or maintain the immune process within the thyroid in Graves' disea se (GD) and Hashimoto's thyroiditis (HT). Quantitative assessment of t he cytokine profile may provide important clues as to the Th1/Th2 bala nce prevailing in these diseases. We analyzed cytokine mRNA expression levels in thyroid tissue samples from 13 patients with GD, 2 with HT, 5 with nontoxic multinodular goiter (NTG), and 4 with thyroid autonom y (nodular = TA(nod) and perinodular = TA(peri) tissue) using multispe cific competitor fragments with primer sequences for IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IFN-gamma, CD25, and CD3 delta-chain mRNA. Pa tients with GD were subdivided into two groups according to their seru m levels of antibodies to thyroperoxidase (anti-TPO: GD(high) > 4000 U /mL, GD(low) less than or equal to 200 U/mL). These levels correlated positively with the CD3 delta-chain mRNA levels (r = 0.83) and with th e T cell infiltration (r = 0.71) as determined by immunohistochemistry . Patients with GD(high) demonstrated 2- to 4-fold higher IL-4 mRNA le vels (as compared to all other investigated groups) and significantly higher IL-10 mRNA levels as compared to HT, GD(low), and TA(nod) patie nts. Patients with GD(high) also had significantly higher levels of IF N-gamma, IL-1 beta, IL-8, and CD25 mRNA as compared to GD(low). The hi ghest IFN-gamma, IL-2, and CD25 mRNA levels were found in HT. The lowe st mRNA levels of all the investigated groups were detected in TA(nod) . No significant differences in IL-6 and IL-8 mRNA levels were found b etween most of the patient groups. In summary, patients with GD(high) showed a shift to a more Th2-driven cytokine pattern. In contrast, the increase mRNA levels of Th1-related cytokines found in HT indicate pr edominantly T cell-mediated cytotoxic processes.