The Effect of Methylprednisolone Pulse Treatment on Cytokine Network in Graves Ophthalmopathy

Abstract

The etiology of Graves ophthalmopathy (GO), representing the most common extrathyroidal manifestation of Graves disease, is multifactorial. Among multiple genetic, environmental, and endogenous factors, cytokines play a critical role in its etiopathogenesis. We studied an effect of glucocorticoid therapy on the serum IL-6, IL-4, and IL-13 levels in 18 GO patients. All the patients presented euthyroid GO with over 4 points according to the CAS classification (range 4-6; mean 4.94). The patients were treated with methylprednisolone (1 g every second day for three times) followed by 6 months oral prednisone (60 mg/day, with gradual reduction). The clinical examination (Clinical Activity Score and the GO severity by modified NOSPECS classification) and measurement of anti-TPO, anti-TG, anti-TSHR (TRAK), IL-6, IL-4, as well as IL-13 serum levels were performed before, after 2 weeks, and after 6 months of the glucocorticoid therapy. Significant serum IL-6 increases (p < 0.001) and moderate serum IL-4 and IL-13 increases (p < 0.05) were found in GO patients compared with healthy controls. After 2 weeks of the therapy, the serum IL-6 levels decreased in majority of the patients, however after 6-month observation, lower serum IL-6 levels were only in 8 patients who seemed to respond clinically to the therapy (mean value of the Clinical Activity Score decreased from 4.5 before the therapy initiation to 1.25 after 6 months of the glucocorticoid therapy). No changes in IL-4 and IL-13 serum levels during the therapy were observed. Statistical analysis revealed a good correlation between serum IL-6 level and the Clinical Activity Score (p < 0.01). Based on the obtained data, we conclude that IL-6 plays an important role in GO. It seems that IL-6 may serve as a useful factor in the inflammatory events of GO.

Function of regulatory T-cells improved by dexamethasone in Graves' disease

“…However, the mechanism by which DEX reduces the relapse rate of GD is not fully understood. DEX is a kind of glucocorticoid usually used in the treatment of Graves' ophthalmopathy (GO) and is one of the most effective medicines (14,15). Some reports showed that Treg cell count increased with DEX treatment in chronic idiopathic thrombocytopenic purpura and other autoimmune diseases (16,17).…”

Thyroid Eye Disease: Pathogenesis and Treatment

“…The most significant finding was a uniform decrease in IL-6 levels after 2 weeks and a sustained decrease after 6 months in 8/18 patients who had responded clinically to the steroids (mean CAS of 1.25). The levels of IL-4 and IL-13 did not have significant trends with treatment [13]. Although Th1- and Th2-like cytokines are involved in the pathogenesis of GD, efforts to correlate the balance in IL-12/IL-5 cytokines in GD patients did not strongly correlate with TED disease activity [4].…”

Feasibility of tomotherapy for Graves’ ophthalmopathy

“…Thus, a high dose of steroid alone or in combination with radiotherapy has been employed successfully to reduce orbital inflammation and the severity of the ophthalmopathy [15,18]. However, longterm steroid administration is associated with significant side effects mainly Cushing's syndrome [18].…”

“…However, longterm steroid administration is associated with significant side effects mainly Cushing's syndrome [18]. Low dose radiotherapy has been demonstrated to be effective in reducing the severity of Graves' ophthalmopathy with lasting results and minimal morbidity [10,15,20,27,33]. The effectiveness of radiotherapy may be limited in severe proptosis with a higher percentage of patients developing disease progression or no improvement following radiotherapy [10,26].…”

“…The beam is usually split in half at the center of the beam (half-beam technique) to avoid beam divergence to the lens inducing severe cataracts [10,15,20,26,27,33]. When the patient has severe proptosis, the half-beam technique (HBT) will underdose the soft tissue and extraocular muscles anterior to the radiation fields which may explain the high failure rates following conventional radiotherapy [20].…”