Serum Levels of Soluble TNFα Receptors (sTNFR1 and sTNFR2) During Corticosteroid Treatment in Patients with Graves' Ophthalmopathy

Abstract

TNFα was shown to play an important role in the autoimmune inflammatory process of Graves' ophthalmopathy (GO). In our previous study we found no significant changes in serum TNFα levels in GO patients. The aim of the present study was to estimate an influence of corticosteroids on serum levels of TNFα receptors (sTNFR1 and sTNFR2) in GO patients and to assess their potential as a guideline of immunosuppressive therapy. We detected serum sTNFR1 and sTNFR2 in three groups of subjects: 18 patients with clinical symptoms of ophthalmopathy [Clinical Activity Score (CAS) ≥ 4, anamnesis of GO ≥ 1 yr], 16 patients with Graves' disease without ophthalmopathy (Gd) and 14 healthy volunteers. Corticosteroid therapy consisted of intravenous infusions of methylprednisolone (MP) and subsequent treatment with oral prednisone (P). The serum samples were collected 24 hours before MP, 24 hours after MP, 14 days of treatment with prednisone and after the end of the corticosteroid therapy. The levels of serum sTNFR1 and sTNFR2 were determined by ELISA. Serum levels of sTNFR1 were significantly higher in GO individuals as compared to the control group (p < 0.01). We have found a significant decrease in sTNFR1 concentration in corticosteroid‐respondent patients (satisfactory clinical effect, decrease of CAS ≥ 1) as compared to the pretreatment values after MP treatment (p < 0.05) and after 14 days of prednisone (p < 0.01). There were significant differences in sTNFR2 level after MP treatment (p < 0.02) and after corticosteroid administration (p < 0.05) between responders and non‐responders. Baseline values of sTNFR1 in GO individuals were positively correlated with CAS (r = 0.6, p < 0.02). Conclusions: TNFα acting through its receptors plays an important role in the pathogenesis of Graves' ophthalmopathy. Moreover, the beneficial influence of corticosteroids on the course of GO may be explained, at least in part, by an inhibition of sTNFR1 and sTNFR2. Measurement of soluble TNFα receptors might potentially serve as an indicator in prognostic estimation of corticosteroids' efficacy.