Immune stimulation in scleroderma patients treated with thalidomide

Scleroderma (SSc) is a fibrosing connective tissue disease that is poorly r esponsive to any treatment, including immune suppression. SSc shares many c haracteristics with chronic graft-versus-host disease (GVHD). Because the i mmunomodulatory drug thalidomide has proven beneficial in chronic GVHD, we studied the immune response and clinical effects of thalidomide in SSc pati ents. We treated 11 SSc patients with thalidomide in an open label, dose es calating, 12 week study. Histologic comparison of skin biopsies showed chan ges in skin fibrosis and an increase in epidermal and dermal infiltrating C D8(+) T cells with thalidomide treatment. in thalidomide-treated SSc patien ts, plasma levels of IL-12 and TNF-alpha increased, while plasma IL-5 and I L-10 levels remained unchanged. These changes were associated with clinical effects, including dry skin, dermal edema, transient rashes, decreased gas troesophageal reflux symptoms, and healing of digital ulcers. When SSc PBMC s activated by anti-CDS mAb were exposed to thalidomide, increases in both production of IL-2, IL-3, GM-CSF, and IFN-gamma and T cell expression of CD 40L were observed. Thalidomide therefore appears to induce immune stimulati on in SSc patients in association with clinical changes. However, it remain s to be shown whether long-term enhancement of immune responses in SSc pati ents is clinically beneficial. (C) 2000 Academic Press.