Endocrine Abstracts (2005) 9 OC38

Anti-TNFa therapy inhibits TNFa-dependent ICAM1 up-regulation in orbital fibroblasts from patients with thyroid associated ophthalmopathy

TJ Cawood1,2, P Moriarty3, L Golden-Mason2, C O'Farrelly2,4 & D O'Shea1


1Department of Endocrinology, St. Vincent's University Hospital, Dublin, Ireland; 2Education and Research Centre, St. Vincent's University Hospital, Dublin, Ireland; 3Royal Victoria Eye and Ear Hospital, Dublin, Ireland; 4The Conway Institute, University College Dublin, Ireland.


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.

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