Interleukin (IL)-18 is a cloned
cytokine that was identified originally as
a factor having potent
interferon (IFN)-gamma-inducing activity on Kupffer cells. First, we analyzed
IL-18 gene expression by reverse transcription-polymerase chain reaction (RT-PCR) in rat thyroid FRTL-5 cells and human thyroid tissue samples. The expression of
IL-18 mRNA in FRTL-5 cells was enhanced by thryoid-stimulating
hormone (TSH) in a dose-dependent manner. 8-Bromo-cyclic
adenosine monophosphate (cAMP) also increased in
IL-18 mRNA levels. Furthermore, TGCT clones that exhibited an increase in intracellular cAMP accumulation showed an increased
IL-18 mRNA signal when compared to controls. Taken together, these data suggested that the effect of TSH on
IL-18 gene expression was mediated by activating
protein kinase A. Treatment of FRTL-5 cells with the
antithyroid drug,
methimazole (MMI), suppressed this stimulatory action of TSH on
IL-18 gene expression. Next, we examined
IL-18 expression in human thyroid tissue derived from patients with autoimmune
thyroid diseases (ATD). RT-PCR and immunohistology demonstrated that human thyroid follicular cells expressed
IL-18. Especially in thyroid tissue from a patient with Hashimoto's
thyroiditis, expression was more diffuse and extensive, generally observed in close relation to a lymphocytic infiltrate. Also,
IL-18 protein was distributed in the same follicles that express Fas-L and
HLA-DR. This study is the first to demonstrate the detection of
IL-18 in the thyroid gland. The frequent expression of
IL-18 in thyrocytes suggests that
IL-18 itself might be a secreted
immunomodulator in ATD.