PROSTAGLANDIN E(2) PRODUCTION BY CHRONIC GRAFT-VERSUS-HOST DISEASE DERMAL FIBROBLASTS

Chronic graft versus host disease (cGVHD) across minor histocompatibil ity barriers is associated with the development of cutaneous fibrosis, disappearance of mast cells and immunosuppression. The idea, which ha s been the basis of our previous and present studies, is that fibrobla sts are not only a target for modulation in cGVHD, but also have effec tor roles in this condition. In the present study we investigated the production of prostaglandin E(2) (PGE(2)) and of collagen by cultured dermal fibroblasts obtained from cGVHD and control mice. Early in the development of the disease (Day 8) cGVHD fibroblasts generated constit utively more PGE(2) (3-fold) than did control fibroblasts. Thereafter, PGE(2) production declined to near normal levels by Day 20 post cGVHD induction. On the other hand, at this time point cGVHD fibroblasts di splayed an enhanced synthesis of collagen as compared to the control f ibroblasts and to earlier time points. Therefore, PGE(2) synthesis app ears to inversely correlate with collagen synthesis by cGVHD fibroblas ts. We propose that fibroblasts may contribute to the development of i mmunosuppression, which characterizes the early phase of cGVHD.