Changes in Th1/Th2 cytokine balance in Graves' disease

Craves' disease (GD) is characterised by hyperthyroidism caused by stimulat ory thyrotropin receptor (TSHR) antibodies. Recent research shows that an i mportant factor in the pathogenesis of autoimmune diseases is the change in the balance between Th1 cytokines, which promote cell mediated immunity, a nd Th2 cytokines, which promote humoral immunity. There are contradictory d ata about this balance shift in GD. Our objective was to determine the Th1/ Th2 cytokine balance shift in patients with newly diagnosed GD, when compar ed to the same balance in healthy controls. We isolated mononuclear cells ( MNC) from the peripheral blood of healthy donors and from patients with new ly diagnosed GD before treatment. The MNC were activated with ionomycin in combination with phorbol 12-myristate 13-acetate (PMA). After 40-hour incub ation, the concentrations of the cytokines produced (IFN-gamma, IL-4, IL-10 , IL-12) in the culture supernatants were measured by ELISA (Endogen, USA). The MNC cultures from patients with GD produced significantly less IL-12 a nd significantly more IL-10 and IL-4 than MNC cultures from healthy control s. All calculated ratios of Th1 against Th2 cytokines in MNC cultures from patients with GD were significantly lower than in MNC cultures from healthy controls. Our results show a systemic shift of cytokine production in pati ents with GD toward the Th2 cytokine response, thus confirming the key role of TSHR antibodies and humoral immunity in the pathogenesis of GD.