Serum cytokines in thyrotoxicosis

Overproduction of thyroid hormones promotes bone resorption in vivo and in vitro, and we have evaluated whether mediators of such effects could includ e the osteotropic cytokines. Previous studies have demonstrated raised seru m interleukin (IL)-6 in thyrotoxic patients, but differentiating the contri bution of the elevated thyroid hormones from that of the autoimmune inflamm ation present in Graves' disease (GD) has been difficult. We undertook a lo ngitudinal study of 34 patients (19-45 yr old) with GD, toxic nodular goite r (TNG), or a history of thyroid carcinoma but no evidence of disease recur rence, receiving sufficient T-4 to suppress TSH. Controls were 12 euthyroid females. The following measurements were made basally and for 6 months aft er carbimazole treatment: serum free T-4, T-3, bone-specific alkaline phosp hatase (b-ALP), IL-6, IL-8, IL-1 beta, tumor necrosis factor-alpha, IL-11, and urinary deoxypyridinoline (Udpd). Compared with controls (IL-6, 1.1 +/- 0.3 ng/L; IL-8, 3.2 +/- 0.8 ng/L), untreated patients with GD and TNG had elevated IL-6 (GD, 7.11 +/- 0.88 ng/L; TNG, 7.30 +/- 0.77 ng/L; P < 0.001) and IL-8 (GD, 10.3 +/- 1.23 ng/L; TNG, 9.81 +/- 1.27 ng/L; P < 0.001). Thes e levels fell after treatment and were then indistinguishable from those in control subjects. Thyroid carcinoma patients on TSH suppressive therapy al so had significantly raised levels of IL-6 (2.5 +/-: 0.42 ng/L) and IL-8 (4 .4 +/- 0.63 ng/L). When data from all the patients were pooled, the levels of IL-6 and IL-8 correlated with serum T-3 and free T-4 but not with Udpd o r b-ALP. IL-1 beta, IL-11, and tumor necrosis factor-alpha were not raised in any patient. The elevations in serum IL-6 and -8 that occur in hyperthyroidism seem to r esult from the chronic effects of thyroid hormone excess rather than the ac companying autoimmune inflammatory condition produced by Graves' thyroid or eye disease. The site of the presumed increased production of IL-6 and -8 is most likely from bone osteoblasts, despite the inability of bone markers (such as Udpd and b-ALP) to correlate with acute changes in thyroid hormon e status produced by antithyroid therapy.