Serum levels of tumor necrosis factor-alpha, soluble intercellular adhesion molecule-1, soluble vascular cell adhesion molecule-1, and soluble interleukin-1 receptor antagonist in patients with thyroid eye disease undergoing treatment with somatostatin analogues.

The aim of this prospective, randomized study was to investigate the serum levels of tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble interleukin-1 receptor antagonist (sIL-1RA) in patients with thyroid eye disease (TED) before and 1 and 3 months after treatment with somatostatin analogues (SM-a). Thirty patients, all with signs and symptoms of TED, were studied. Twenty-two patients (13 females) had active eye disease with a clinical activity score (CAS) > or = 4 (patients with active disease [PA]) and 8 patients (5 females) had inactive TED with CAS < or = 3 (patients with inactive disease [PI]). All PA patients had a positive orbital octreoscan, whereas PI patients had a negative one. Fifteen patients from the PA group were selected randomly and received SM-a (PA-S subgroup), while the remaining 7 patients were used as control subgroup (PA-C), received neither therapy, nor placebo. From the 15 patients who received SM-a (PA-S), 6 received octreotide (OCT) and 9 lanreotide (LRT). TED was reevaluated using the CAS 1 and 3 months after the initiation of SM-a treatment. Ten healthy individuals (6 females) were used as controls (group C). We found an increase in the basal levels of TNF-alpha (14.2 +/- 7.1 pg/mL), sICAM-1 (809.1 +/- 167.0 ng/mL), and sIL-1RA (542.1 +/- 259.0 pg/mL) in PA patients as a total group compared with the PI (1.6 +/- 1.9, 676.8 +/- 73.4, 267.6 +/- 152.8, respectively) group and C (1.9 +/- 1.4, 598.0 +/- 126.2, 258.6 +/- 155.1, respectively). The basal levels of TNF-alpha (13.3 +/- 8.3 pg/mL) and sIL-1RA (533.7 +/- 308.9 pg/mL) in PA-S as well as in PA-C (16.0 +/- 2.9, 560.2 +/- 107.3, respectively) subgroups were also increased compared with PI patients and C (1.9 +/- 1.4 and 258.6 +/- 155.1, respectively). The same was true for sICAM-1 when baseline levels compared with C (817.1 +/- 187.3 and 791.9 +/- 123.5, respectively vs. 598.0 +/- 126.2 ng/mL). After SM-a, serum levels of sICAM-1 and sVCAM-1 were decreased significantly 1 (781.2 +/- 205.9, 1,193.5 +/- 511.8 ng/mL) and 3 months (786.8 +/- 199.6, 1,122.1 +/- 225.3 ng/mL) after the initiation of treatment. In conclusion, serum levels of TNF-a, sICAM-1, and sIL-1RA were elevated in patients with active TED compared to controls. Furthermore, sICAM-1 and sVICAM-1 levels declined during the treatment with SM-a in patients with active TED.

Soluble interleukin-1 receptor antagonist serum levels in smokers and nonsmokers with Graves' ophthalmopathy undergoing orbital radiotherapy.

Interleukin-1 (IL-1) plays an important role in the pathogenesis of Graves' ophthalmopathy (GO). Impaired antagonism of the proinflammatory cytokine IL-1 by the naturally occurring IL-1 receptor antagonist (IL-1RA) has been implicated in the initiation and perpetuation of various autoimmune diseases and may play a role in the evolution of GO. Cigarette smoking appears to adversely affect the course of GO. We have evaluated the course of IL-1 alpha, IL-1 beta, and soluble IL-1RA (sIL-1RA) serum levels in smokers and nonsmokers with GO undergoing orbital radiotherapy (OR). We prospectively studied the eye status of 27 randomly selected patients (mean age 47.3 +/- 11.0 yr; 20 females; 18 smokers) with active, moderately severe GO before and 3 and 6 months following OR, respectively. None had received any previous treatment for GO, and all patients were kept euthyroid on carbimazole. Serum concentrations of IL-1 alpha, IL-1 beta, and sIL-1RA were measured using highly sensitive enzyme linked immunosorbent assay systems. Baseline sIL-1RA levels were negatively correlated with the number of cigarettes smoked before and following OR (P < 0.0001). Patients with no or minor therapeutic response to OR (n = 8), all of whom were smokers, revealed mean baseline sIL-1RA levels of 114 +/- 85 pg/mL, which increased to 172 +/- 103 pg/mL at 3 months and 149 +/- 96 pg/mL at 6 months after initiation of OR, respectively. By contrast, patients with a good clinical response (n = 19, 9 nonsmokers), revealed significantly higher baseline sIL-1RA levels at 294 +/- 148 pg/mL (P = 0.004), which increased to 845 +/- 668 pg/mL at 3 months (P = 0.01) and 634 +/- 337 pg/mL at 6 months (P < 0.001), respectively, following initiation of OR. Serum concentrations of IL-1 alpha IL-1 beta were below 3.9 pg/mL in all patients with GO who were studied, and were not correlated with gender, age, smoking status, clinical course, or outcome. Low baseline levels and impaired surge of sIL-1RA serum levels following OR were strongly correlated with smoking status and a less favorable therapeutic outcome in patients with active, moderately severe GO. Measurement of sIL-1RA may contribute to predict the therapeutic response to OR in patients with active, moderately severe GO. Strategies designed to raise local or systemic concentrations of sIL-1RA may be of benefit to patients with GO.