Soluble interleukin-2 receptor is a thyroid hormone-dependent early-response marker in the treatment of thyrotoxicosis

Abstract

Thyrotoxic patients exhibit increased levels of immune activation molecules (soluble interleukin-2 receptor [sIL-2R], intercellular adhesion molecule-1 [ICAM-1], and endothelial-leukocyte adhesion molecule-1 [ELAM-1]) in serum, although the clinical significance of these measurements remains unclear. In a randomized 4-week study, we have recently shown that in the treatment of hyperthyroidism, the combination of cholestyramine and methimazole (MMI) resulted in faster lowering of serum thyroid-hormone levels than did MMI alone. Stored serial serum samples from patients participating in this randomized treatment trial were analyzed for sIL-2R, soluble ICAM-1 (sICAM-1), and soluble ELAM-1 (sELAM-1). The levels of all three molecules were elevated in patients with hyperthyroidism. Although the levels of sICAM-1 and sELAM-1 remained elevated through the 4-week follow-up period in both groups of patients, the sIL-2R levels (normal levels, 1.0 to 4.2 ng/ml) decreased significantly in the 10 patients who received cholestyramine in addition to MMI (week 0, 14.2 ؎ 1.5 ng/ml; week 2, 10.8 ؎ 1.2 ng/ml; week 4, 8.9 ؎ 1.5 ng/ml). In eight patients who received MMI alone, sIL-2R decreased less rapidly (week 0, 12.3 ؎ 1.4 ng/ml; week 2, 12.3 ؎ 1.3 ng/ml; week 4, 10.9 ؎ 1.3 ng/ml). sICAM-1 and sELAM-1 were elevated at baseline but did not decrease during therapy. In the former group, free thyroxine and free triiodothyronine decreased faster. These data show that levels of sIL-2R in serum, but not those of sICAM-1 and sELAM-1, may be of clinical use in the early follow-up evaluation of medically treated patients.

The relationship between thyroid function, serum monokine induced by interferon gamma and soluble interleukin-2 receptor in thyroid autoimmune diseases

“…In agreement with this, a strong positive correlation of sIL-2R with FT4 and negative correlation with TSH were found. The results are in agreement with the literature and show that serum concentrations of sIL-2R in GD patients are related to the thyroid function rather than to activation of immunity [14].…”

Soluble Tumour Necrosis Factor-α Receptor I and Interleukin-6 as Markers of Activity in Thyrotoxic Graves' Disease

“…Wakelkamp and colleagues have also observed elevated serum levels of both sTNF-receptors in patients with Graves' disease exhibiting euthyroid states [27]. For comparison, sIL-2R serum levels may be enhanced in Graves' thyroid disease due to a hypermetabolic stage leading to increased thyroid function as well as by thyroid autoimmune processes [23], as recent data suggested a role for thyroid hormone in the activation of immune cells and the release of cytokines and sIL-2R in the serum [24]. In contrast to the presented data on sIL-2R, we found sTNF-RI to be statistically significantly correlated to TRAb, indicating a closer relation with the autoimmune mechanisms of Graves' disease compared to sIL-2R in these studies.…”

Soluble Interleukin 2 Receptors' Levels Versus Thyroid Hormones Levels in Nonthyroidal Disease

“…The patients of this study were not immunocompromised and made an uneventful recovery, so in this setting, we can also speculate (given the small overall variations), a relation between thyroid hor mones and sIL-2R in the low-T3 syndrome. Since the measurement of sIL-2R has already been proposed as an indicator of disease activity in Graves' disease (11) and an early response marker in thyrotoxicosis' treatment (5), further relevant studies can be envisaged, in order to assess the behavior and clinical utility of sIL-2R levels versus thyroid function parameters in non-thyroidal disease.…”

“…Normal peripheral blood mononuclear cells and certain lines of T-and B-cell origin release, after its membrane expression, a soluble form of interleukin-2 receptor (sIL-2R); this appears to be a consequence of cellular activation of various cell types that may play a role in the regulation of the immune response (1,2) . Patients with autoimmune diseases, haematologic malignant diseases or overt thyroid disease often show high sIL-2R serum levels (3,4,5), however the course of sIL-2R levels in non-thyroidal disease affecting thyroid function has not been adequately explored. Recent studies have shown that patients with tuberculosis (TB) present with low to normal free and total triiodothyronine levels, which rapidly elevate after anti-TB treatment (6,7,8).…”