Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans

Abstract

Cytokines, such as tumor necrosis factor-alpha and interleukin-1 beta (IL-1 beta), alter thyroid hormone metabolism, and may be involved in the pathogenesis of the euthyroid sick syndrome. Both cytokines also induce the production of IL-6. To assess whether IL-6 itself modulates thyroid hormone metabolism, we studied the acute and chronic effects of recombinant human IL-6 (rhIL-6) on thyroid hormone concentrations in patients with renal cell cancer. In the first study protocol, plasma thyroid hormone concentrations were measured during a 4-h infusion of rhIL-6 (150 micrograms) or, on another day, during infusion of saline (control; n = 8). There were no effects of rhIL-6 infusion on T4, free T4, or thyroid hormone-binding index. However, rhIL-6 induced a significant decrease in the plasma concentrations of TSH (P < 0.001) and T3 (P < 0.001) compared with those in the control study, associated with an increase in rT3 concentrations (P < 0.001). In the second study, a dose of 150 micrograms rhIL-6 was administered sc for 42 consecutive days (n = 8). Weekly assessment of thyroid hormone and TSH concentrations showed a decrease in the T3 concentration (P < 0.001) and a transient increase in rT3 (P < 0.01) and free T4 concentrations (P < 0.01). There were no changes in T4 concentrations during chronic administration of rhIL-6. It is concluded that IL-6 induces major changes in thyroid hormone metabolism and may be another pathogenetic factor in the euthyroid sick syndrome.

The role of cytokines and cortisol in the non-thyroidal illness syndrome following acute myocardial infarction

“…In vitro experiments with human thyrocytes or in vivo with rats have shown that TNF-a, IL-1b, IL-6 and interferon-a (IFN-a) inhibit several thyroid cell functions (4). Administration of recombinant IL-6 to humans induced significant decrease in serum T 3 and TSH concentrations in association with an increase in serum rT 3 , and no changes in T 4 and FT 4 concentrations (19). In agreement with this were our findings of a strong positive correlation between IL-6 and T 3 , and the negative correlation between IL-6 and rT 3 or rT 3 /T 3 ratio, although TSH and IL-6 were not correlated.…”

Role of cytokines in the pathogenesis of the euthyroid sick syndrome

“…The effects of IL-6 were evaluated after either acute or chronic administration in patients with renal cancer (101). The acute (4 h) intravenous administration of 150 mg IL-6 to eight patients was followed by a significant decrease in serum TT 3 and TSH concentrations, with an increase in serum rT 3 levels and no change in serum TT 4 and FT 4 concentrations (101) ( Table 4).…”

Relationship between circulating cytokine levels and thyroid function following bone marrow transplantation

“…In cultured human thyrocytes, IL-6 and TNF-a inhibited TSH-stimulated T 3 secretion, 30,31 and the administration of IL-6 or TNF-a in humans was followed by a significant decrease in serum T 3 and TSH concentrations, and an increase in serum rT 3 levels. 32,33 Neutralization of the effects of IL-6 by anti-IL-6 antibody was reported in animals. 34 In a recent study, Nagaya et al 35 found that NF-kB activation by TNF-a is involved in the pathogenesis of ESS and that the inhibition of NF-kB activation could help prevent a decrease in serum T 3 levels, and thus ameliorate ESS.…”