Vascular disease in scleroderma. Endothelial T lymphocyte-fibroblast interactions.

The accumulated body of evidence suggests a role for a cell-mediated immune mechanism in the pathogenesis of scleroderma vascular disease. The most likely target for immune injury is either the endothelial cell itself or components of its basal lamina, which include type IV collagen and laminin. Whatever the specific target, the net effect is persistently altered endothelial cell dysfunction. However, the molecular basis for the development of endothelial cell injury is not known. Direct investigations of perivascular infiltrating cells have not been possible yet; published studies have focused on the in vitro effects of peripheral blood mononuclear cells and selected cytokines on endothelial cell behavior and function. Understanding the multiple cellular effects of various cytokines on endothelial cells may further the knowledge of the vascular disease. Systematic study of interactions between endothelial cells and cells of the immune system may provide the molecular basis for vascular injury and open yet unidentified avenues for therapy. Furthermore, monitoring parameters of endothelial cell injury may help to define the disease in an earlier and more meaningful fashion. Circulating levels of EC products such as von Willebrand factor, plasminogen activator, and prostacyclin/thromboxane metabolites may permit a precise definition of disease activity and assist the clinician in monitoring responses to therapy.