A stimulatory thyrotropin receptor antibody (M22) and thyrotropin increase interleukin-6 expression and secretion in Graves' orbital preadipocyte fibroblasts.

Background: Patients with Graves' ophthalmopathy (GO) have circulating autoantibodies directed against the thyrotropin receptor (TSHR) and elevated levels of the proinflammatory cytokine interleukin-6 (IL-6) in both serum and orbital tissues. We hypothesized that these autoantibodies might increase IL-6 expression and secretion in preadipocyte fibroblasts and adipocytes from patients with GO, and thus directly impact the clinical activity of the disease.

Methods: IL-6 mRNA levels were measured in cultures of GO orbital preadipocytes (n = 3) treated during adipocyte differentiation with a monoclonal stimulatory TSHR antibody (M22; 10 ng/mL), IL-6 (1 ng/mL), or TSH (10 U/L).

Evidence for enhanced Thy-1 (CD90) expression in orbital fibroblasts of patients with Graves' ophthalmopathy.

Background: Thy-1 is a surface protein that defines functionally distinct subpopulations of fibroblasts, with those lacking the antigen being capable of adipogenesis. Because increased fat cell development is a hallmark of the orbit in Graves' ophthalmopathy (GO), we wished to compare baseline Thy-1 expression in orbital fibroblasts from GO patients and normal individuals, and determine whether levels of the protein might be impacted by adipogenesis following peroxisome proliferator activator-gamma ligation.

Methods: Orbital adipose/connective tissue specimens were obtained from euthyroid patients undergoing orbital decompression surgery for severe GO (n = 9) and from normal individuals (n = 9).