AUGMENTED INTERLEUKIN-6 SECRETION IN COLLAGEN-STIMULATED PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM PATIENTS WITH SYSTEMIC-SCLEROSIS

Background: Systemic sclerosis is an autoimmune disease that is associ ated with excessive fibroblast proliferation and collagen deposition i n various tissues, Interleukin-6 (IL-6) is produced by fibroblasts, ac tivated T and B lymphocytes, which maybe involved in the pathogenesis of systemic sclerosis. Objective: This study was performed in order to determine whether IL-6 could be detected specifically in collagen-sti mulated peripheral blood mononuclear cells from patients with systemic sclerosis. Methods: We clinically evaluated seven patients with syste mic sclerosis for disease duration and organ involvement and analyzed in vitro the ability of their peripheral blood mononuclear cells and t hose of disease-free controls, in the presence of concanavalin A, huma n type I collagen, and the mast eel mediator, heparin to secrete IL-6 spontaneously by a sensitive ELISA. Results: Interleukin-6 production by nonspecific stimulation with concanavalin A did not differ between patients with systemic sclerosis and controls; however, collagen stimu lation significantly increased IL-6 production in patients with system ic sclerosis; mean 1728 pg/mL versus a mean of 386 pg/mL in controls P = <.05). Collagen-stimulated IL-6 levels >2000 pg/mL were obtained in 86% of patients with systemic sclerosis compared with none in the con trols. In patients with systemic sclerosis with a shorter disease dura tion, greater spontaneous as well as collagen- and heparin-stimulated IL-6 production was observed, whereas decreased IL-6 levels were noted with longer disease duration (>21 years). Conclusions: The results of this study suggest that peripheral blood mononuclear cells from patie nts with systemic sclerosis are specifically sensitized to human type I collagen to produce increased levels of IL-6, which may play a role in the pathogenesis in this fibrotic disorder.