The clinical role of serum concentrations of selected cytokines: IL-1β, TNF-αand IL-6 in diagnosis of autoimmune thyroid disease (AITD) in children

Abstract

Chronic autoimmune thyroiditis (cAIT) leads to hypothyroidism due to T cell-mediated cytotoxicity in most cases. By contrast, Graves' disease (GD) with thyrotropin receptor stimulatory autoantibodies cause hyperthyroidism. Cytokines play a crucial role in modulating immune response in both disorders. The aim of study was to evaluate the concentrations of cytokines: IL-1β, TNF-α and IL-6 in these two opposite clinical and hormonal thyroid diseases. The study group consisted of 64 children, 44 newly diagnosed, untreated children with cAIT (n = 22; with hypothyroidism) and GD (n = 22; hyperthyroidism), and the control group of 20 healthy children. Cytokine concentrations were evaluated using the ELISA technique. The studied groups of children did not differ significantly in concentrations of IL-6 (p = 0.48) and TNF-α (p = 0.067). In children with hypothyroidism, we found significantly higher concentrations of IL-1β (median 2.16 pg/ml, IQR 0.87) compared to hyperthyroidism (median 1.39 pg/l, IQR 1.27) (p < 0.01) and the control group (median 1.88 pg/ml, IQR 1.04) (p < 0.05). The results of ROC curve analysis demonstrated the usefulness of IL-1β (AUC = 0.77, p = 0.003) and TNF-α (AUC = 0.691, p = 0.034) as diagnostic parameters in cAIT which enable discrimination of children with autoimmune thyroid disease from healthy individuals. Concentrations of these markers are increased in autoimmune hypothyroidism. We found no significant sex differences in the tested parameters. In conclusion, IL-1β and TNF-α may be considered as markers of hypothyroidism, and could efficiently discriminate between healthy and autoimmune hypothyroid children. Significantly higher concentrations of IL-1β in children with hypothyroidism may be used to distinguish children with cAIT from GD patients.

Iron metabolism in patients with Graves’ hyperthyroidism

“…New‐onset GH can be interpreted as a form of acute‐phase or inflammatory reaction, but markers of inflammation and inflammatory cytokines in our patients were not affected neither by thyroid function nor by smoking status. These findings are in concordance with other studies where circulating serum cytokines are unchanged in GH patients or only partially elevated …”

Changes in serum hepcidin according to thyrometabolic status in patients with Graves’ disease

“…Additionally, polymorphisms in the IL-6 gene were found to be correlated with GD predisposition (21). It may be presumed that IL-6 overproduction in patients with GD stimulates the JAK2-STAT3 pathway to synthesize hepcidin, which consequently affects iron homeostasis and haematological parameters (12,22).…”

Changes in glucose‐lipid metabolism, insulin resistance, and inflammatory factors in patients with autoimmune thyroid disease

“…13,14 Cytokines, such as IL-1beta, TNF-alpha, and IL-6, play a crucial role in modulating immune response in autoimmune disorder and therefore are considered as markers of hypothyroidism. 15 As hypothyroidism occurs in patients, the clearance rate of LDL-C is reduced. Moreover, the activity of lipoprotein lipase is inhibited by the thyroid hormones, ultimately resulting in the increase in serum TC level.…”