The putative role of cytokine-orbital fibroblast interactions in the pathogenesis of thyroid-associated ophthalmopathy

Abstract

Orbital fibroblasts appear to possess phenotypic attributes that set them apart from fibroblasts derived from the skin. Among the differences between orbital and dermal fibroblasts are responses to inflammatory mediators such as the lymphokine, leukoregulin. This lymphokine causes a marked upregulation of hyaluronan synthesis in orbital fibroblasts. The magnitude of this cellular response is considerably greater than that observed in dermal fibroblasts. Leukoregulin also increases the expression of plasminogen activator inhibitor type-1 and prostaglandin E₂ synthesis dramatically in orbital fibroblasts. The author hypothesizes that these anatomic site-selective actions of leukoregulin in orbital fibroblasts represent the molecular basis for the two central features of tissue reorganization associated with Graves' ophthalmopathy, disordered accumulation of glycosaminoglycans and intense inflammation. His findings begin to define a potentially useful model for the design of specific therapeutic modalities.

Key Words:

• Leukoregulin
• prostaglandins
• glycosaminoglycans