Cytokines in the evolution of Graves' ophthalmopathy

Infiltration of the retroocular space by inflammatory cells and the accumulation of glycosaminoglycans are histological characteristics of Graves' ophthalmopathy. Various cytokines, released by infiltrating immunocompetent cells and resident connective tissue cells, play a pivotal role in the evolution of this disease. The predominant cytokines secreted by orbital T cells during the course of the disease may govern the activity and stage of the local autoimmune process. Cytokine effects of potential relevance to the pathogenesis of Graves' ophthalmopathy include their ability to stimulate orbital fibroblasts to proliferate and secrete excess quantities of glycosaminoglycans. The edema associated with these hydrophilic macromolecules is directly responsible for many of the characteristic clinical features of the disease. In addition, certain cytokines induce or enhance the expression on orbital fibroblasts of immunomodulatory proteins. We review current evidence supporting the notion that cytokines are central to the development and evolution of Graves' ophthalmopathy.