INCREASED MITOGENIC ACTIVITY OF SCLERODERMA SERUM - INHIBITORY EFFECTOF HUMAN RECOMBINANT INTERFERON-GAMMA

Objectives-To investigate the role of platelet activation in the devel opment of systemic sclerosis and the role of interferon-gamma (IFN gam ma) in the inhibition of mitogenic activity induced by whole blood ser um of patients with systemic sclerosis. Methods-The mitogenic activity of whole blood serum in the absence or presence of different concentr ations of LFN gamma (a potent inhibitor of induced collagen synthesis in dermal fibroblasts) and platelet-poor plasma derived serum were tes ted on human dermal fibroblasts by measuring incorporation of [H-3]thy midine. Platelet activation was determined by quantification of plasma beta-thromboglobulin (beta-TG) using a beta-TG radioimmunoassay kit. Results-The mitogenic activity was significantly increased in whole bl ood serum and in platelet-poor plasma derived serum of the patients co mpared with controls. In contrast, no significant increase in beta-TG concentration was observed in scleroderma platelet-poor plasma compare d with control. Recombinant human IFN gamma had a greater inhibitory e ffect on the mitogenic activity induced by whole blood serum of patien ts than on that produced with control sera, at any concentration of IF N gamma tested. Conclusions-Our results suggest that mitogenic activit y observed in the plasma of sclerodermic patients could originate from cells other than platelets and could be involved in the development o f fibrosis. The potent inhibitory effect of IFN gamma on this prolifer ative activity may account for the beneficial effect of this cytokine in the treatment of progressive systemic sclerosis.