Increased adipose tissue secretion of interleukin-6, but not of leptin, plasminogen activator inhibitor-1 or tumour necrosis factor alpha, in Graves' hyperthyroidism

Abstract

Objective: This study was designed to investigate adipose tissue secretion of interleukin-6 (IL-6), leptin, tumour necrosis factor alpha (TNF-a) and plasminogen activator inhibitor-1 (PAI-1) in Graves' hyperthyroidism. Design: We studied 10 patients before and during (after 8 weeks) anti-thyroid treatment for Graves' hyperthyroidism and 16 healthy, euthyroid control subjects. Methods: Plasma levels of thyroid hormones and serum/plasma levels of IL-6, leptin, TNF-a and PAI-1 were analysed. Subcutaneous fat biopsies were taken for subsequent measurement of IL-6, leptin, TNF-a and PAI-1 protein secretion. Results: In patients with Graves' disease, the anti-thyroid treatment resulted in significant reductions of plasma thyroxine and triiodothyronine levels. No differences in serum concentration or adipose tissue secretion of leptin or TNF-a were observed either before, as compared with during, anti-thyroid treatment, or in comparison with euthyroid controls. In contrast, plasma PAI-1 activity, but not adipose tissue secretion of PAI-1, was increased both in Graves' disease before as compared with during anti-thyroid treatment ðP ¼ 0:01Þ and in thyrotoxic patients compared with euthyroid controls ðP ¼ 0:0001Þ: Finally, adipose secretion of IL-6 was increased both before (8-fold, P ¼ 0:001) and during (6-fold, P , 0:0001) treatment as compared with control subjects. Accordingly, serum concentration of IL-6 was also increased by about 50% in thyrotoxic patients as compared with healthy controls ðP ¼ 0:03Þ: Conclusions: In Graves' hyperthyroidism regardless of thyroid status, adipose tissue secretion of IL-6, but not of leptin, TNF-a or PAI-1, is markedly increased in comparison with euthyroid controls. This suggests that autoimmune thyroidal disorder may regulate adipose tissue release of IL-6.

IL-1β Induces IL-6 Expression in Human Orbital Fibroblasts: Identification of an Anatomic-Site Specific Phenotypic Attribute Relevant to Thyroid-Associated Ophthalmopathy

“…For instance, cytokine levels are elevated in thyroid tissue from patients with active disease (64,65). Wahrenberg et al (24) have reported that adipose tissues from these individuals release several-fold higher levels of IL-6 than do similar tissues from control subjects. Circulating IL-6 levels have also been found to be elevated in Graves' disease (17)(18)(19)(20)(21)(22).…”

“…Its expression can be enhanced substantially in differentiated 3T3F442A adipocytes by ␤-adrenergic activation, an effect also seen in cultures derived from s.c. breast tissue and abdominal wall (43,44). The finding that IL-6 mRNA levels correlate positively with tissue volumes in TAO (23) suggests that a promotion by IL-6 of adipogenesis could underlie the expansion of orbital fat in TAO (1,24).…”

“…IL-6 and soluble IL-6R, like several other important cytokines, have been found to be elevated in patients with Graves' disease (17)(18)(19) and those with TAO (20 -23). IL-6 protein can be detected in s.c. fat in these patients (24). Hiromatsu et al (23) found that extraocular eye muscle and orbital fat from patients with TAO express IL-6 mRNA and that orbital volumes correlated positively with transcript levels.…”

Iodine-131 therapy alters the immune/inflammatory responses in the thyroids of patients with Graves' disease

“…In patients with GD, IL-6 is produced by infiltrating immune cells and thyrocytes (25). Serum IL-6 levels in patients with GD have been reported to be significantly higher than those in healthy controls (21,26). However, the clinical significance of serum IL-6 levels remains controversial.…”

The effect of thyroid hormones on the white adipose tissue gene expression of PAI-1 and its serum concentration

“…Some reports have described an increase in serum PAI-1 concentration in hyperthyroidism, whereas others did not detect any differences (7)(8)(9).…”