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*

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-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.

The prognostic value of Pro-Calcitonin, CRP and thyroid hormones in secondary peritonitis;A single-center prospective study

“…Prognosis of patients with this syndrome is correlated with serum levels of T3 and T4. [21][22][23][24] In our study, low T3, T4 levels among groups with higher mortality and complication rates were found.…”

Effects of proinflammatory cytokines on anterior pituitary 5'-deiodinase type I and type II

“…In rat FRTL-5 thyroid cells, basal and TSH-induced D1 activity is inhibited by IL-1 , IL-6 and TNF , and D1 mRNA levels are reduced by IL-1 and IL-6, but not by TNF (Hashimoto et al 1995). In mouse liver D1 is stimulated by IL-1 (Fujii et al 1989) but is not affected by TNF (Ozawa et al 1988). However, in rat liver D1 is inhibited by TNF (Pang et al 1989, Tang et al 1995 in vivo but stimulated by TNF , IL-1 and IL-6 in vitro in rat liver 1 cells (Davies et al 1997).…”

Role of cytokines in the pathogenesis of the euthyroid sick syndrome

“…These changes, mostly related to decreased thyroid hormone binding to T 4 -binding prealbumin, were accompanied by a decrease in both basal and TRHstimulated TSH levels, while rT 3 remained unchanged and 5 0 -DI was apparently unaffected (76). The effect of IL-1 on 5 0 -DI activity is not unequivocal, since an increase in liver 5 0 -DI activity was also reported in IL-1-treated mice (77). Likewise, a stimulation of 5 0 -DI activity was reported in the brain cortex of IL-1-treated rats (75).…”