Interleukin 6 effects on the pituitary-thyroid axis in the rat.
It has been postulated recently that cytokines, and in particular interleukin 1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha), may have a role in the pathogenesis of the changes of serum thyroid hormone concentrations that are encountered in patients with non-thyroidal illness (NTI). Many of the IL-1 and TNF-alpha effects are believed to be mediated by the induction of IL-6 synthesis, which might, therefore, represent an important mediator of thyroid hormone changes in NTI. To address this problem, male Wistar rats were injected subcutaneously with 2.5 micrograms of recombinant human IL-6 (rhIL-6, in 500 microliters of saline solution), with 2.5 micrograms of rhIL-6 preincubated with 100 microliters of anti-IL-6 neutralizing antibody or with saline solution alone (control group). Administration of rhIL-6 resulted in a significant decrease of thyroxine (T4) from 82 +/- 4 nmol/l (mean +/- SEM) to a nadir of 33 +/- 3 nmol/l (p < 0.0001) after 48 h, and of triiodothyronine (T3) from 1.6 +/- 0.1 to 0.8 +/- 0.1 nmol/l after 48 h (p < 0.0001). A slight decrease in serum T4 and T3 concentrations also was observed in the control group, but the lowest values (T4, 66 +/- 3 nmol/l; T3, 1.2 +/- 0.1 nmol/l) were significantly higher (p < 0.0001) than in IL-6-treated rats. The IL-6-induced changes could be prevented by preincubation of rhIL-6 with its neutralizing antibody.(ABSTRACT TRUNCATED AT 250 WORDS)
Bartalena
L
L
Istituto di Endocrinologia, University of Pisa, Italy.
Grasso
L
L
Brogioni
S
S
Martino
E
E
D000818:Animals; D007037:Hypothyroidism / Q000097:blood / Q000139:chemically induced; D007279:Injections, Subcutaneous; D015850:Interleukin-6 / Q000494:pharmacology*; D008297:Male; D008713:Methimazole; D010902:Pituitary Gland / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins; D013961:Thyroid Gland / Q000187:drug effects*; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood; D014285:Triiodothyronine, Reverse / Q000097:blood
D015850:Interleukin-6; D011994:Recombinant Proteins; D014284:Triiodothyronine; D008713:Methimazole; D014285:Triiodothyronine, Reverse; D013972:Thyrotropin; D013974:Thyroxine