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More Than IL-6 in Graves’ Disease?—Authors’ Response¹

Università degli Studi di Parma Parma, Italy L. E. Braverman University of Massachusetts Worcester, MA 01655

The observations made by Çelik et al. related to our paper on "Increased Serum Concentrations of Interleukin-6 (IL-6) and Soluble IL-6 Receptor (sIL-6R) in Patients with Graves’ Disease" (1) are perhaps based on misinterpretation of some of the data presented. The group of newly diagnosed hyperthyroid Graves’ disease (GD) patients consisted of 31 patients who were tested before antithyroid treatment (MMI) and were followed until they became euthyroid, within 3–12 months, at which time thyroid function tests and serum IL-6/sIL-6R values were reassessed. This group differs from groups of 12 and 19 patients who were restudied at 12 months of therapy and who were in remission or who had relapsed, respectively. Thus, we do not believe that the statistical analysis applied, i.e. the Wilcoxon signed rank test, would result in a type II error because the groups compared are of sufficiently large size. In addition, while serum concentrations of sIL-6R declined from 940 to 726 pmol/L after MMI, those of IL-6 did not. Although the assay employed measured both free IL-6 and IL-6 bound to the soluble receptor, the molar ratio of sIL-6R/IL-6 in the circulation is about 10,000:1. It would seem plausible that the observed changes in sIL-6R concentrations did not bear a relationship with those of IL-6. In interpreting the lack of association of either IL-6 or sIL-6R secretion with remission or relapse of GD, measurement of TSH receptor autoantibody activity would have been helpful. We found the data of Çelik et al. on the increased secretion of TNF- in autoimmune hyperthyroidism of interest (2). On the other hand, we believe that the IL-6/sIL-6R system cannot be ruled out as marker of thyroid autoimmunity. We have recently presented evidence that, in euthyroid GD patients, serum IL-6 concentrations are significantly increased in the serum of those patients with circulating anti-thyroid peroxidase (TPO) antibodies and ophthalmopathy during the active inflammatory phase (3). The understanding of the role of this cytokine in autoimmunity certainly deserves further study.

Footnotes

¹ Address correspondence to: Dr. Lewis E. Braverman, Division of Endocrinology and Metabolism, University of Massachusetts Medical Center, Worcester, Massachusetts 01655.

Received December 30, 1996.

References

1. Salvi M, Girasole G, Pedrazzoni M, et al. 1996 Increased serum concentrations of interleukin-6 (IL-6) and soluble IL-6 receptor in patients with Graves’ disease. J Clin Endocrinol Metab. 81:2976–2979.[Abstract/Free Full Text]
2. Çelik I, Akalin S, Erbas T. 1995 Serum levels of interleukin-6 and tumor necrosis factor-alpha in hyperthyroid patients before and after propylthiouracil treatment. Eur J Endocrinol. 132:668–672.[Abstract/Free Full Text]
3. Salvi M, Girasole G, Pedrazzoni M, et al. 1996 Increased serum interleukin concentrations in euthyroid patients with active thyroid associated ophthalmopathy and antiperoxidase antibodies. 69th Annual Meeting of the American Thyroid Association, San Diego, November 13–17. Thyroid. 6 [Suppl.1] S68 (Abstract 134).\.

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