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.
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-1 alpha or IL-1 beta at a dose of 0.015-1 microgram/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 microgram/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-alpha 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.
Fujii
T
T
Department of Medicine, Tokyo Women's Medical College, Japan.
Sato
K
K
Ozawa
M
M
Kasono
K
K
Imamura
H
H
Kanaji
Y
Y
Tsushima
T
T
Shizume
K
K
D000818:Animals; D001835:Body Weight; D004435:Eating; D007375:Interleukin-1 / Q000494:pharmacology*; D007453:Iodide Peroxidase / Q000378:metabolism*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011994:Recombinant Proteins / Q000494:pharmacology; D012709:Serum Albumin / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D007375:Interleukin-1; D011994:Recombinant Proteins; D012709:Serum Albumin; D013963:Thyroid Hormones; D014284:Triiodothyronine; D014285:Triiodothyronine, Reverse; D013972:Thyrotropin; D007453:Iodide Peroxidase; D013974:Thyroxine