Graves’ disease (GD) is an organ-specific autoimmune disease caused by the stimulation of thyroid-stimulating hormone receptor (TSHR) autoantibodies and is characterized by hyperthyroidism, goiter, and exophthalmos.1, 2 Although the disease pathomechanism remains unclear, several factors play an important role in the initiation and progression of GD, including inflammation.3 Cytokines are secreted by immune and endocrine cells and are responsible for various immunological and inflammatory functions.4 Studies have proven that cytokines are produced and secreted by thyroid follicular cells, and they have proven to take part in coordinating the immune reaction in GD pathogenesis.4, 5, 6 Although GD is predominantly characterized by a Th2 cytokine profile, with intrathyroidal lymphocytes secreting cytokines, such as interleukin (IL)-4, IL-5, IL-10, and IL-13 to support antibody-mediated immune responses, the role of cytokines in GD is highly complex. Thyrocytes not only have the capacity to produce cytokines but also actively respond to them. Such responses include regulating several markers, such as IL-1, IL-6, IL-8, transforming growth factor (TGF)-β, IL-16, CXCL-10, CXCL-19, and others, which are modulated upon their activation.7 Furthermore, since TSHR-antibody (Ab) is produced through the immune-mediated mechanism, the elevated amount of pro-inflammatory cytokines secreted by thyroidal cells may be associated with the level of TSHR-Ab production.

IL-6 is a pleiotropic cytokine with both pro- and anti-inflammatory properties.8, 9, 10, 11, 12, 13 Classic signaling via membrane-bound IL-6 receptor (IL-6R) is mainly considered for the regenerative functions of IL-6.14 On the other hand, trans-signaling through soluble IL-6R (sIL-6R) is a well known pro-inflammatory mediator.9, 12 However, in both cases, the biological activities of IL-6 are mediated through a complex with signal-transducing gp130 receptor (gp130), which activates intracellular signaling pathways.14 Overall, nearly 70% of IL-6 forms an IL-6:sIL-6R complex and directly binds to the gp130, while the rest circulate in the blood or bind to the membrane IL-6R.15 sIL-6R and soluble gp130 (sgp130) constitutively exist in human serum, and sgp130 has been recognized as natural inhibitors of IL-6 trans-signaling.14

The involvement of the IL-6:sIL6R:sgp130 complex has been identified in various autoimmune conditions, such as rheumatoid arthritis and Crohn's disease.16, 17 Although it has been shown that IL-6 methylation level is correlated with the intractability of GD,18 conflicting reports on the level of systemic IL-6 in GD have been identified.19, 20, 21, 22 Furthermore, there are limited studies evaluating the level of sgp130 in GD. Additionally, unbalanced immune and inflammatory conditions have been proposed as one of the possible mechanisms of autoimmunity. Various IL, including IL-10, seem to participate in GD pathogenesis by modulating IL-6 and TSHR-Ab production.23, 24 Therefore, this study aims to investigate the serum levels of IL-6, sIL-6R, sgp130, and IL-10 in GD patients in an attempt to determine the risk factors that may affect the development of GD.