Chronic cyclosporine-induced autoimmune disease in the rat: a new experimental model for scleroderma

The pathogenesis of scleroderma is still elusive, although autoimmune mechanism involvement has been suggested. The present study was designed to investigate whether or not rat scleroderma would appear as one of the symptoms in a recently described model for autoimmune disease. The model is based on manipulation or reconstitution of the immune system after lethal irradiation and syngeneic bone marrow transplantation by temporary administration of the immunosuppressive drug cyclosporine-A. Withdrawal of cyclosporine-A 6-12 wk after bone marrow transplantation gives rise to autoimmune reactions causing clinical pathology similar to graft-versus-host disease. We discuss the chronic phase of this disease, approximately 30 wk after cyclosporine-A was withheld at that time-about one-third of the rats had developed histologic skin lesions comparable to those seen in patients with scleroderma. Therefore, we propose this model as a new, experimental autoimmune model for scleroderma in humans.