CYTOKINES IN THYROID EYE DISEASE - POTENTIAL FOR ANTICYTOKINE THERAPY

Interactions between between orbital fibroblasts and immunocompetent c ells that infiltrate or reside within the orbit are thought to be impo rtant in the pathogenesis of thyroid eye disease (TED). These interact ions are mediated primarily by cytokines; interferon-gamma, tumor necr osis factor-alpha, interleukin-1 alpha and leukoregulin are of particu lar interest in this regard. These mediators induce or enhance the in vitro expression of immunomodulatory proteins in orbital fibroblasts, and stimulate proliferative and metabolic activities of these cells. T he stimulation by particular cytokines of glycosaminoglycan synthesis in orbital fibroblasts is an important factor in the development of th e clinical disease. A similarly important pathophysiological role for cytokines has been defined in rheumatoid arthritis. In this disease, t he chronic erosive changes in the cartilage and bone of the joints res ult from cytokine-stimulated production of collegenases and other neut ral proteases by synovial cells and articular chondrocytes. Advances i n the understanding of the pathogenesis of rheumatologic joint disease has led to treatment trials aimed at immune-modulation, including tri als of anticytokine therapy. Lessons learned in early clinical trials using these biological therapies in the treatment of rheumatoid arthri tis can be applied to studies of similar agents in the treatment of TE D.