Role of cytokines in the pathogenesis of thyroid-associated ophthalmopathy

Thyroid-associated ophthalmopathy (TAO) is generally considered to be an autoimmune disorder associated with Graves' disease. However, the nature of autoantigen or mechanism of the development of ophthalmopathy remains unclear. In the present review we focus the accumulating evidence on roles of cytokines in the orbital tissues from patients with TAO and animal models. From the analysis of T-cell clones, T helper 1 (T(H)1)-like clones were predominant in cultures from patients with recent onset hyperthyroidism and T(H)2-like clones were predominant in culture form patients with more remote onset hyperthyroidism. T(H)1-like cytokine profiles are predominant in eye muscle tissue and related to the eye muscle enlargement, while T(H)2-like cytokine profiles are predominant in orbital fat tissue from patients with TAO and negatively related to orbital volume. Therefore, T(H)1-like cytokines, proinflammatory cytokines, may play a role on the development of eye muscle component of TAO in the acute stage. T(H)2-like cytokines, anti-inflammatory cytokines, may play protective role in the chronic stage of TAO. The studies using animal models suggest the genetic background is involved in the pathogenesis of TAO. The studies on polymorphism of the cytokine genes support the proinflammatory role of T(H)1-like cytokines and protective role of T(H)2-like cytokines.