Effects of acute and chronic interleukin-6 administration on thyroid hormone metabolism in humans.
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.
Department of Internal Medicine, Academic Medical Center, University of Amsterdam, The Netherlands.
J M
JM
Stouthard
T
T
van der Poll
E
E
Endert
P J
PJ
Bakker
C H
CH
Veenhof
H P
HP
Sauerwein
J A
JA
Romijn
D002292:Carcinoma, Renal Cell / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism; D013974:Thyroxine / Q000097:blood / Q000378:metabolism; D014284:Triiodothyronine / Q000097:blood / Q000378:metabolism
D015850:Interleukin-6; D011994:Recombinant Proteins; D014284:Triiodothyronine; D013972:Thyrotropin; D013974:Thyroxine