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Effect of Interleukin-1 (IL-1) on Thyroid Hormone Metabolism in Mice: Stimulation by IL-1 of Iodothyronine 5'-Deiodinating Activity (Type I) in the Liver^*

TORU FUJII, KANJI SATO, MINORU OZAWA, KEIZO KASONO, HIDEHITO IMAMURA, YOSHIHARU KANAJI, TOSHIO TSUSHIMA and KAZUO SHIZUME

Departments of Medicine (T.F., K.Sa., M.O., K.K., H.I., T.T., K.Sh.) and Surgery (Y.K.), Institute of Clinical Endocrinology, Tokyo Women's Medical College Kawada-cho 8-1
Research Institute of the Foundation for Growth Science in Japan (K.Sa., T.T., K.Sh.) Wakamatsu-cho, Sinjuku-ku, Tokyo, Japan

Address requests for reprints to: Kanji Sato, Institute of Clinical Endocrinology, Tokyo Women's Medical College, Kawada-cho 8-1, Shinjuku-ku, Tokyo 162, Japan.

Abstract

To elucidate the mechanism by which the low T₃ and low T₄ syndrome occurs in patients with infection, recombinant human interleukin-1 (IL-1) was administered to mice, and their thyroid hormone metabolism was studied.

Continuous sc infusion of IL-la or IL-1/8 at a dose of 0.015- 1 Mg/day for 3 days decreased food intake and serum T₄, T₃, and rT₃ concentrations in a dose-dependent manner. In pair-fed control (PFC) mice, serum T₄ and T₃ also decreased, but rT₃ was reciprocally increased. The T₃/T₄ ratio was greater in IL-1- treated mice than in PFC mice. Although food intake was decreased by 65% in IL-1-treated mice (1 /xg/day) compared with that in fed control mice, type I iodothyronine 5'-deiodinating activity in liver was significantly increased compared with that in fed control mice. Furthermore, the T₃ and T₄ responses to TSH were greatly diminished in IL-1-treated mice.

These findings suggest that IL-1 directly inhibited the effect of TSH on the thyroid gland and decreased the serum concentrations of T₄ and T₃, and that an increase in type I iodothyronine 5'-deiodinating activity in livers of IL-1-treated mice may account for the greater T₃/T₄ ratio and lower serum rT₃ concentration than those in PFC mice. Since tumor necrosis factor-a has a similar effect, we speculate that both cytokines may be synergistically involved in the altered thyroid hormone metabolism in mice (decreased serum T₄, T₃) and rT₃ concentrations) and hypercatabolism in a febrile state. (Endocrinology 124:167–174,1989)

Footnotes

^* This work was supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (61570563), a research grant from the Foundation for Growth Science in Japan, the Kato Memorial Trust for Nambyo Research, and a research grant from the U.S.-Japan Malnutrition Panel, 1987.

Present address: Third Department of Internal Medicine, Nagoya City University Medical School, Nagoya, Japan.

Received June 17, 1988.

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