Immune Stimulation in Scleroderma Patients Treated with

Scleroderma (SSc) is a fibrosing connective tissue disease that is poorly responsive to any treatment, including immune suppression. SSc shares many characteristics with chronic graft-versus-host disease (GVHD). Because the immunomodulatory drug thalidomide has proven beneficial in chronic GVHD, we studied the immune response and clinical effects of thalidomide in SSc patients. We treated 11 SSc patients with thalidomide in an open label, dose escalating, 12 week study. Histologic comparison of skin biopsies showed changes in skin fibrosis and an increase in epidermal and dermal infiltrating CD8 T cells with thalidomide treatment. In thalidomide-treated SSc patients, plasma levels of IL-12 and TNF-a increased, while plasma IL-5 and IL-10 levels remained unchanged. These changes were associated with clinical effects, including dry skin, dermal edema, transient rashes, decreased gastroesophageal reflux symptoms, and healing of digital ulcers. When SSc PBMCs activated by anti-CD3 mAb were exposed to thalidomide, increases in both production of IL-2, IL-3, GM-CSF, and IFN-g and T cell expression of CD40L were oberved. Thalidomide therefore appears to induce imune stimulation in SSc patients in association with linical changes. However, it remains to be shown hether long-term enhancement of immune responses n SSc patients is clinically beneficial. © 2000 Academic