Thyroid Associated Ophthalmopathy (TAO) is an autoimmune inflammatory condition that usually occurs in patients with Graves' disease. Current treatment for TAO is inadequate and anti-cytokine agents may represent a potential new therapeutic strategy. Orbital fibroblasts are central to the disease mechanism, and have been shown by immunohistochemisty to up-regulate adhesion molecule ICAM1 expression in response to certain cytokines including TNFalpha.
In this study we explored the hypothesis that anti-TNFalpha antibody could block TNFalpha-dependent ICAM1 expression in orbital fibroblasts from patients with TAO.
Human orbital fibroblasts were taken at surgery from 3 patients with chronic TAO, and 1 patient without TAO. Orbital fibroblast cultures were established and grown in tissue culture. Fibroblasts were transferred to 6-well plates, grown to confluence, serum starved overnight and then exposed to TNFalpha (0.01ng/ml and 1ng/ml) and/or anti-TNFalpha antibody (Adalimumab 50ug/ml) for 6 hours before being harvested. Cells were stained for flow cytometry analysis using ICAM1 antibody (anti-human CD54) and mouse antibody for control.
TNFalpha up-regulated ICAM1 expression in a dose-dependent manner in fibroblast cultures from both normal and TAO patients. Adalimumab inhibited TNFalpha-dependent ICAM1 expression in cells from patients with TAO (mean reduction in ICAM1 expression in response to 1ng/ml TNFalpha of 64%, 95% CI 26 to 102%, P<0.02).
In vitro, the anti-TNFalpha antibody Adalimumab inhibits TNFalpha-dependent up-regulation of ICAM1 expression in orbital fibroblasts from patients with and without TAO. This supports the hypothesis that anti-TNFalpha therapy may attenuate the inflammatory response and represent a useful new therapeutic strategy for TAO.
04 - 06 Apr 2005
British Endocrine Societies