Serum cytokines in thyrotoxicosis.

Abstract

Overproduction of thyroid hormones promotes bone resorption in vivo and in vitro, and we have evaluated whether mediators of such effects could include the osteotropic cytokines. Previous studies have demonstrated raised serum interleukin (IL)-6 in thyrotoxic patients, but differentiating the contribution of the elevated thyroid hormones from that of the autoimmune inflammation present in Graves' disease (GD) has been difficult. We undertook a longitudinal study of 34 patients (19-45 yr old) with GD, toxic nodular goiter (TNG), or a history of thyroid carcinoma but no evidence of disease recurrence, receiving sufficient T4 to suppress TSH. Controls were 12 euthyroid females. The following measurements were made basally and for 6 months after carbimazole treatment: serum free T4, T3, bone-specific alkaline phosphatase (b-ALP), IL-6, IL-8, IL-1beta, 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). These levels fell after treatment and were then indistinguishable from those in control subjects. Thyroid carcinoma patients on TSH suppressive therapy also 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 T3 and free T4 but not with Udpd or b-ALP. IL-1beta, 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 result from the chronic effects of thyroid hormone excess rather than the accompanying 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 hormone status produced by antithyroid therapy.