Interleukin-6 (IL-6) inhibits thyroid function in the presence of soluble IL-6 receptor in cultured human thyroid follicles.

Abstract

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.

• Authors: K Yamazaki, E Yamada, Y Kanaji, K Shizume, D S Wang, N Maruo, T Obara, K Sato
• Journal: Endocrinology (Endocrinology) Vol. 137 Issue 11 Pg. 4857-63 (Nov 1996) ISSN: 0013-7227 [Print] United States
• PMID: 8895357 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, CD
• DNA Primers
• Interleukin-6
• Iodides
• Iodine Radioisotopes
• Receptors, Interleukin
• Receptors, Interleukin-6
• Triiodothyronine
• Thyrotropin
• Thyroxine

Topics

• Analysis of Variance
• Antigens, CD (physiology)
• Base Sequence
• Cells, Cultured
• DNA Primers
• Dose-Response Relationship, Drug
• Humans
• Interleukin-6 (pharmacology)
• Iodides (metabolism)
• Iodine Radioisotopes
• Polymerase Chain Reaction
• Receptors, Interleukin (physiology)
• Receptors, Interleukin-6
• Signal Transduction
• Thyroid Gland (drug effects, immunology, metabolism)
• Thyrotropin (pharmacology)
• Thyroxine (biosynthesis)
• Triiodothyronine (biosynthesis)