Serum cytokines levels in Graves' disease

Abstract

Objective: The aim of the study was to look at the serum cytokines profile in newly diagnosed thyrotoxic patients with Graves' disease and to compare their cytokine levels with those of normal control subjects. Furthermore, the levels of T4, being an indicator of the severity of thyrotoxicosis, were also correlated with the Th1/Th2 and proinflammatory cytokines in Graves' disease patients.

Methods: Serum IFN-gamma (Th1), IL-10 (Th2), inflammatory cytokines including IL-6, TNF-alpha, sCD23 and sIL-2R cytokine levels were measured in 28 patients with Graves' thyrotoxicosis and in 30 normal controls.

Results: In Graves' disease patients, the levels of IFN-gamma (mean 142.1 +/- 29.53 units/ml), IL-10 (mean 583.8 +/- 253.3 pg/ml) and IL-4 (mean 132.4 +/- 44.52 pg/ml) were significantly higher than their corresponding levels in controls: IFN-gamma (mean 31.6 +/- 2.08 units/ml, P<0.001), IL-10 (mean 69.8 +/- 31.72 pg/ml, P<0.001) and IL-4 (mean 46.44 +/- 11.53 pg/ml). There was a marked increase in proinflammatory cytokines in Graves' disease patients: levels of IL-6 (481.5 +/- 192.3 pg/ml) and TNF-alpha (30.69 +/- 16.7 pg/ml) were significantly higher than those of normal controls for IL-6 (63.81 +/- 21.72 pg/ml, P<0.001) and TNF-alpha (8.81 +/- 1.72 pg/ml, P<0.001). Similarly the levels of sCD23 (mean 164 +/- 67.03 ng/ml) and sIL-2R (mean 2131 +/- 461.1 units/ml) were significantly higher in GD patients than in the control group (mean 31.24 +/- 11.53 ng/ml, P<0.001) and (mean 345.53 +/- 121.75 units/ml, P< 0.001) for sCD23 and sIL-2R. Furthermore, in thyrotoxic Graves' disease patients, we detected a positive correlation between free T4 and sIL-2R levels (r2 = 0.81, P<0.00), but no significant correlation was found between T4 and the other measured cytokines.

Conclusion: The elevated serum cytokines of Graves' thyrotoxic patients reflect the activation and interplay of mixed Th1 and Th2 cells which may be consistent with long standing inflammatory and destructive processes of thyroid gland. The clinical severity of hyperthyroidism in Graves' patients only correlated with sIL-2R.