Enhanced interleukin 6 production by cultured fibroblasts from patients with systemic sclerosis in response to platelet derived growth factor

Objective. The pathophysiology of systemic sclerosis (SSc) is poorly understood, but recent studies indicate the involvement of cytokines in the functional changes of SSc fibroblasts. We investigated interleukin 6 (IL-6) production by dermal fibroblasts from patients with SSc. Methods. Fibroblast cultures were established from affected skin of patients with SSc and from skin of healthy controls. IL-6 in supernatants from cultured fibroblasts was measured using a specific IL-6 ELISA. Results. SSc fibroblasts, starved in serum-free medium, produced only a small amount of IL-6. However, IL-6 production by SSc fibroblasts dramatically increased when the cells were cultured in serum-containing medium. Human whole blood serum was more effective than human platelet-poor plasma derived serum in the enhancement of IL-6 production by SSc fibroblasts. Platelet derived growth factor (PDGF)-AA and PDGF-BB, a major growth factor in serum, induced significant IL-6 production by SSc fibroblasts. In contrast, in normal fibroblasts, much less response to PDGF-BB and almost no response to PDGF-AA were observed. Expression of PDGF receptors on SSc fibroblasts was not significantly different from normal fibroblasts. However, IL-1 receptor antagonist (IL- 1ra), when added in the medium, significantly inhibited the PDGF-induced IL- 6 production by SSc fibroblasts. Conclusion. PDGF stimulates IL-6 production by SSc fibroblasts. The enhanced IL-6 production in response to PDGF is due in part to autocrine IL-1 of SSc fibroblasts. These abnormalities of fibroblasts may play an important role in the inflammatory and immunological processes of SSc.