EFFECTS OF METHOTREXATE ON GLYCOSAMINOGLYCAN PRODUCTION BY SCLERODERMA FIBROBLASTS IN CULTURE

Objective-To determine the effects of increasing concentrations of met hotrexate on the proliferation and glycosaminoglycan (GAG) synthesis o f cultured dermal fibroblasts from patients with scleroderma. Methods- Cultured dermal fibroblasts from nine patients with scleroderma and ni ne normal volunteers were grown for 72 hours in media containing vario us concentrations of methotrexate. The GAG synthesis in each cell was measured after incubating the fibroblasts with [H-3]glucosamine and [S -35]sulphate. Results-A negative correlation was found between the con centration of methotrexate and numbers of fibroblasts from patients wi th scleroderma and normal controls. A positive correlation was found b etween GAG synthesis in each cell, as measured by [H-3]glucosamine and [S-35]sulphate incorporation, and increasing methotrexate concentrati ons in fibroblasts from patients with scleroderma and normal controls. Conclusions-These data indicate increased GAG synthesis in scleroderm a and normal fibroblasts with increasing concentrations of methotrexat e. Therefore the reported beneficial effect of methotrexate on skin fi brosis in scleroderma is most probably not the result of direct inhibi tion of GAG synthesis by fibroblasts.