British Journal of Dermatology (1990) 123, 339-346. Pentoxifylline inhibits the prohferation of human fibroblasts derived from keloid, scleroderma and morphoea skin and their production of collagen, glycosaminoglycans and fibronectin B.BERMAN AND M.R.DUNCAN Department of Dermatology, University of California, Davis School of Medicine, Davis, and the Dermatology Service, Veterans Administration Medical Center, Martinez, California, U.S.A. Accepted for publication 11 April 1990 SUMMARY Pentoxifylline, an analogue of the methylxanthine theobromine, inhibits the proliferation and certain biosynthetic activities of fibroblasts derived from normal human skin. Fibroblasts from the skin of patients with keloids, scleroderma and morphoea were cultured in vitro in the presence and absence of pentoxifylline (ioo-iooo /ig/ml) to determine whether it inhibits fibroblast proliferation and the production of collagen, glycosaminoglycans (GAG), fibronectin and collagenase activity. The exposure of subconfluent fibroblast cultures to pentoxifylline resulted in non-lethal, dose-dependent reductions in serum-driven fibroblast proliferation, with 1000 ngjxaX pentoxifylline virtually negating the proliferative effect of serum on the cells. The fibroblasts assayed as confluent cultures produced reduced amounts, by up to 95%, of collagen and GAG, dependent on the concentration of pentoxifylline, both in the presence and absence of serum. Pentoxifylline similarly inhibited the fibronectin production by keloid and scleroderma fibroblasts, but had no effect on collagenase activity. Fibroblasts are the major cell type responsible for maintaining the integrity of the extracellular matrix found in the dermis of the skin and other connective tissues. Under basal conditions, the fibroblasts maintain the extracellular matrix by synthesis and degradation of its components.' This balance of synthesis and degradation is only transiently altered during normal repair processes such as occurs in wound healing, and abnormalities in matrix component metabolism may be responsible for the excessive fibrosis that occurs in scleroderma,^ morphoea,^ cutaneous Correspondence: Dr Brian Berman, Dermatology Service (190), VA Medical Center, 150 Muir Road, Martinez, California 94553, U.S.A. 339