Mirakian et al. question our recent results, which suggest that thyrocyte survival during thyroid autoimmunity depends on differential effects of TH1 and TH2 cytokines1. Thyrocyte destruction in autoimmune thyroiditis is a slow process that lasts several years. We hypothesized that in thyroid autoimmunity the balance between life and death in thyrocytes depends on the predominance over the time of TH2 and TH1 cytokines, whose action is not restricted to immune cells but involves direct modulation of key molecules responsible for survival or death of target cells1.

As we discussed in our article, GD and HT are the two extremes of a wide clinical spectrum of thyroid autoimmunity that includes a series of mixed forms showing various degrees of tissue destruction. This heterogeneity may explain some conflicting results published in the literature.

However, before publishing our hypothesis1, we analyzed cytokine expression in thyroid tissues from eight GD and eight HT patients. As described in our article, although the cytokine pattern is not "black and white", this analysis showed a clear prevalence of TH2 cytokines in GD and TH1 in HT1 (and our unpublished data). These results were not published entirely because, considered in line with other published data2,3, they were redundant.

Concerning the points specifically raised by Mirakian et al. in relation to their previous findings4, we have the following comments. (i) In contrast to their data, IL-10 production has been clearly documented by others5 in thyroids from patients with GD and not in thyroids from control patients. (ii) Mirakian et al. found IL-10 expression only in 1/2 HT-affected thyroids4. (iii) In contrast to what they claim, Mirakian et al. have shown that IL-10 was present only in the thyroid of the HT patient with the longest duration of disease (6 years)4. (iv) The protective role of IL-10 in autoimmune thyroiditis has been demonstrated in vivo6.

Finally, we did not mention Bcl-2 in our article1 because its overexpression in thyrocytes does not exert a clear protective effect during Fas-induced apoptosis in thyrocytes (our unpublished data).

See TH1 and TH2 cytokine control of thyrocyte survival in thyroid autoimmunity by R. Mirakianand and the Control of target cell survival in thyroid autoimmunity by T helper cytokines via regulation of apoptotic proteins by Giorgio Stassi