Transforming growth factor ß1 (TGFß1) and vascular endothelial growth factor (VEGF) in the blood of healthy people and patients with Graves' orbitopathy--a new mechanism of glucocorticoids action?

ABSTRACT

INTRODUCTION: The first part of this paper is related to healthy people and presents concentrations of TGFß1 and VEGF in blood (with and without dividing data with respect to sex), their single measurement values (at 8 am), Mean Daily Concentrations (MDC), Area Under the Curves (AUC; total daily secretion), and circadian rhythm. The second part of the work is related to Graves' orbitopathy (GO). The aim of the study were 1) to determine the physiological pattern of TGFß1 and VEGF secretion; 2) to compare the serum TGFß1 and VEGF circadian profile in newly diagnosed thyreotoxic patients with active GO and healthy controls (H); and 3) to estimate the influence of high-dose intravenous methylprednisolone pulse therapy (MP) on TGFb1 and VEGF blood levels in GO. MATERIAL AND METHODS: Twenty-two healthy (H) subjects and 16 hyperthyroid GO patients were treated with MP (6 g/14 days) and followed up by ophthalmological assessment. Blood was collected before and after 2 weeks MP-therapy. TGFß1 and VEGF levels were determined by the ELISA method. RESULTS: No difference was observed in the concentrations of TGFß1 and VEGF in the blood of healthy women and men - in further analysis, a combined healthy male and female cohort was used (H). While the absence of circadian rhythms in the concentrations of TGFß1 and VEGF allows the application of a single measurement approach, MDC and AUC measurements were found to be more precise. There were no differences in TGFß1 MDC/AUC between GO and H. VEGF MDC/AUC in GO were higher than in H. MP-therapy increased TGFb1 MDC/AUC, thus in GO after MP, the TGFß1 MDC/AUC were higher than in H. There were no differences in VEGF MDC/AUC during MP-therapy. MP-therapy was effective in 15/16 patients. CONCLUSIONS: 1. MP-therapy increases MDC and AUC of TGFß1. The effectiveness of MP-therapy in patients with active GO may be related to its influence on TGFß1 concentrations in blood. The results suggest the existence of a new mechanism of glucocorticoids action, consisting of an increase in the secretion of TGFß1.2. The elevated serum VEGF in thyreotoxic patients with active GO may reflect long-standing autoimmune processes in orbital and thyroid tissues and intensified angiogenesis in the thyroid gland.