Interleukin-6 (IL-6) inhibits thyroid function in the presence of soluble IL-6 receptor in cultured human thyroid follicles.
Interleukin-6 (IL-6), a pleiotropic cytokine, is postulated to be involved in the pathogenesis of sick euthyroid syndrome, although the direct in vitro effects of IL-6 on human thyroid function are controversial. Because IL-6 signal can be transduced when the complex of IL-6 and soluble IL-6 receptor (sIL-6R) binds to gp 130, an IL-6 signal transducer, we studied the effects of IL-6 and sIL-6R on thyroid function, using human thyroid follicles obtained from patients with Graves' disease. IL-6 alone had no inhibitory effect on TSH-induced thyroid function (125I incorporation and organic 125I release), even at supraphysiological concentrations. However, in the presence of physiological concentrations of sIL-6R (100 ng/ml), IL-6 inhibited thyroid function dose dependently and completely, accompanied with the decreased ratio of 125I-T3/125I-T4 not only in the thyroid follicles but also in the culture medium. Thyroid follicles did not secrete sIL-6R but produced IL-6 constitutively. Consistent with these findings, sIL-6R inhibited thyroid function slightly at high concentrations. Furthermore, RT-PCR analyses revealed that human thyroid follicles expressed the messenger RNAs for IL-6 and gp130 but scarcely messenger RNA for IL-6R. These in vitro findings suggest that IL-6 alone hardly affects thyroid function in thyroid follicles in which IL-6R gene is scarcely expressed. However, because sIL-6R is present abundantly in serum, IL-6 in vivo would be capable of inhibiting the synthesis and release of T4 and, to a greater extent, T3 from the thyroid gland. These in vitro findings are at least partly related to the development of sick euthyroid syndrome.
Yamazaki
K
K
Kanaji Hospital, Tokyo, Japan.
Yamada
E
E
Kanaji
Y
Y
Shizume
K
K
Wang
D S
DS
Maruo
N
N
Obara
T
T
Sato
K
K
D000704:Analysis of Variance; D015703:Antigens, CD / Q000502:physiology*; D001483:Base Sequence; D002478:Cells, Cultured; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015850:Interleukin-6 / Q000494:pharmacology*; D007454:Iodides / Q000378:metabolism*; D007457:Iodine Radioisotopes; D016133:Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000502:physiology*; D019947:Receptors, Interleukin-6; D015398:Signal Transduction; D013961:Thyroid Gland / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000096:biosynthesis*; D014284:Triiodothyronine / Q000096:biosynthesis*
D015703:Antigens, CD; D017931:DNA Primers; D015850:Interleukin-6; D007454:Iodides; D007457:Iodine Radioisotopes; D018123:Receptors, Interleukin; D019947:Receptors, Interleukin-6; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine