Objective. In this prospective study, we investigated whether the development of interferon-alfa (IFN-)-related autoimmune thyroiditis (IFN-AT) was correlated with the sequential changes of cytokine pattern induced by the IFN- in the peripheral lymphocytes.

Patients and methods. We enrolled 18 HCV+ patients who developed IFN-AT, of whom 8 with euthyroidism [IFN-AT(Eu)] and 10 patients with thyroid dysfunction [IFN-AT(Dy)]. Twenty HCV+ patients without IFN-AT acted as control group (Co-HCV+). Intracellular expression of IFN- and IL-4 was evaluated by multicolour flow-cytometry analysis in peripheral lymphocytes in vitro stimulated by PMA (25 ng/ml) and ionomycin (1 µg/ml), in presence of monensin (5 µM).

Results. At the appearance of thyroid disease, both IFN-AT(Eu) and IFN-AT(Dy) patients showed a significant increase of IFN- expression in CD3+CD56+ and CD3-CD56+ cells but not in CD4+ and CD8+ cells. At this time-point, IFN-AT(Eu) but not IFN-AT(Dy) patients showed also an increase of IL-4 expression in CD3+CD56+ cells and CD4+ cells. Six months later, IFN-AT(Eu) patients maintained high expression of IL-4 in CD4+ and CD3+CD56+ cells, without any further increase in IFN- expression. By contrast, IFN-AT(Dy) patients showed an increase of IFN- expression in CD4+ and CD8+ cells, with a concomitant decrease of IL-4 expression in CD4+ cells.

Conclusions. Type-2 immune response is activated early and specifically in patients with IFN-AT who remain euthyroid throughout the follow-up. In patients developing thyroid dysfunction, by contrast, is predominant the type-1 immune response that seems to occur earlier in innate than in acquired immune system.