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Effects of Tumor Necrosis Factor-/Cachectin on Thyroid Hormone Metabolism in Mice^*

MINORU OZAWA, KANJI SATO, DOO CHOL HAN, MASANOBU KAWAKAMI, TOSHIO TSUSHIMA and KAZUO SHIZUME

Department of Medicine (M.O., K.S., D.H., T.T., K.S.), Institute of Clinical Endocrinology, Tokyo Women's Medical College Kawada-cho 8-1, Shinjuku-ku, Tokyo 162
Research Institue of the Foundation for Growth Science in Japan (K.S., T.T., K.S.) Wakamatsu-cho, Shinjuku-ku, Tokyo 162
National Medical Center (M.K.) Toyama, Shinjuku-ku, Tokyo 162, 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 low T₃ and low T₄ syndrome occurs in patients with acute or chronic infection or malignancy, recombinant human tumor necrosis factor- (TNF-)/cachectin (TNF) was administered ip to mice and thyroid hormone metabolism was studied. Since administration of TNF caused a decrease in food intake and body weight, all experiments were performed using pair-fed control (PFC) mice. Administration of TNF at a dose of 1–100 Mg/day for 3 days decreased serum T₄, T₃, and rT₃ concentrations in a dosedependent manner. In PFC mice, serum T₄ and T₃ also decreased, but rT₃ was significantly increased. T₃/T₄ ratio was greater in TNF-treated mice than in PFC mice. Type I iodothyronine- 5'-deiodinating activity in the liver was significantly decreased in PFC mice but not in TNF-treated mice. The effect of TNF was reversible and could be abolished by boiling the cytokine. Furthermore, T₃ and T₄ response to TSH was greatly diminished in TNF-treated mice in comparison with PFC mice. These findings suggest that TNF directly inhibited the effect of TSH on the thyroid gland and decreased the serum concentrations of T₄ and T₃. Although TNF decreased food intake and body weight in TNF-treated mice, it did not decrease type 15'- deiodinating activity in the liver, resulting in a greater T₃/T₄ ratio and lower serum rT₃ concentration than those in PFC mice. W speculate that TNF is at least partly involved in the altered thyroid hormone metabolism (decreased serum T₄, T₃, and rT₃ concentrations) caused by infections in mice. (Endocrinology 123: 1461–1467,1988)

Footnotes

^* This work was presented in part at the 60th Meeting of the Japan Endocrine Society Meeting, Tokyo, Japan, November 1987. Supported by Grants-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (61570563, 62570305), a research grant from the Foundation for Growth Science in Japan, and a research grant from the United States-Japan Malnutrition Panel, 1987.

Present address: Saitama Medical College, Kawagoe, Saitama, Japan.

Received March 21, 1988.

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