Immunoregulatory proteins and cytokines in the blood of patients with Graves' disease

Abstract

Immunoregulatory proteins (alpha-2-macroglobulin, lactoferrin) actively participate in inflammatory and autoimmune processes, affect synthesis and transport of hormones and cytokines, and control cell proliferation and apoptosis. However, the role of these proteins in the pathogenesis of Graves' disease (GD) is poorly understood. Objective - the study objective was to determine blood levels of alpha-2-macroglobulin (α2-MG), lactoferrin (LF), and cytokines (TNF-α, IL-6, IL-8, and IFN-γ) in GD. We determined blood levels of TSH, free T4, TSH receptor antibodies, TNF-α, IL-6, IL-8, IFN-γ, and LF by ELISA as well as α2-MG by quantitative rocket immunoelectrophoresis in 50 patients with decompensated and compensated (4-6 months and 1.5-2 years after treatment onset) GD and 25 healthy females (control group). GD clinically manifested by body weight l in 84% of patients, sinus tachycardia in almost all patients, paroxysmal atrial fibrillation in 18% of cases, endocrine ophthalmopathy in 12% of patients, and neurological changes. In decompensated GD, there was a statistically significant increase in levels of IFN-γ, IL-6, and α2-MG and an especially significant increase in levels of IL-8 and LF. At 4-6 months after treatment onset, clinical manifestations were stopped in all patients, levels of IL-6 and α2-MG decreased, but the concentrations of TSH receptor antibodies (TSHR-Abs), IL-8, IFN-γ, and LF remained elevated. At 1.5-2 years, levels of the studied proteins and cytokines did not differ from those in the control group. An increase in blood levels of IL-8, LF, IL-6, and α2-MG in incident or recurrent GD and a decrease in the levels during treatment confirm involvement of immunoregulatory proteins in pathogenesis of the disease.