Increased mitogenic activity of scleroderma serum: Inhibitory effect of human recombinant interferongamma

Abstract

Objectives-To investigate the role of platelet activation in the development of systemic sclerosis and the role of interferon- gamma (IFN γ) in the inhibition of mitogenic activity induced by whole blood serum ofpatients with systemic sclerosis. Methods-The mitogenic activity ofwhole blood serum in the absence or presence of different concentrations of IFN-y (a potent inhibitor of induced coliagen synthesis in dermal fibroblasts) and platelet-poor plasma derived serum were tested on human dermal fibroblasts by measuring incorporation of [3HIthymidine. Platelet activation was determined by quantification of plasma i-thromboglobulin (β-TG) using a β-TG radioimmunoassay kit. Results-The mitogenic activity was significantly increased in whole blood serum and in platelet-poor plasma derived serum of the patients compared with controls. In contrast, no significant increase in β-TG concentration was observed in scleroderma platelet-poor plasma compared with control. Recombinant human IFN-γ had a greater inhibitory effect on the mitogenic activity induced by whole blood serum of patients than on that produced with control sera, at any concentration ofIFNγ tested. Conclusions-Our results suggest that mitogenic activity observed in the plasma of sclerodermic patients could originate from cells other than platelets and could be involved in the development of fibrosis. The potent inhibitory effect of IFN-y on this proliferative activity may account for the beneficial effect of this cytokine in the treatment of progressive systemic sclerosis.