Augmented interleukin-6 secretion in collagen-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis.

Abstract

Background: Systemic sclerosis is an autoimmune disease that is associated with excessive fibroblast proliferation and collagen deposition in various tissues. Interleukin-6 (IL-6) is produced by fibroblasts, activated 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-stimulated peripheral blood mononuclear cells from patients with systemic sclerosis.

Methods: We clinically evaluated seven patients with systemic sclerosis for disease duration and organ involvement and analyzed in vitro the ability of their peripheral blood mononuclear cells and those of disease-free controls, in the presence of concanavalin A, human type I collagen, and the mast cell 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 stimulation significantly increased IL-6 production in patients with systemic 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 controls. In patients with systemic sclerosis with a shorter disease duration, 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 patients 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.