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

Abstract

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.