Interleukin-6 (IL-6) induces the proliferation of synovial fibroblastic cells in the presence of soluble IL-6 receptor

Abstract

A number of investigators have reported that there are detectably elevated levels of interleukin-6 (IL-6) and soluble IL-6 receptor (sIL-6R) in the synovial fluids of rheumatoid arthritis (RA) patients. However, the precise role of IL-6 and sIL-6R in the pathogenesis of RA remains unclear. In the present study we examined whether IL-6 and/or sIL-6R could induce the proliferation of synovial fibroblastic cells (SFC) obtained from a RA patient. Co-existence of IL-6 and sIL-6R induced SFC proliferation without needing any further stimulation. This proliferation was completely blocked by either anti-IL-6 or anti-sIL-6 antibody. In contrast, neither IL-6 nor sIL-6R alone induced SFC proliferation. Although sIL-6R alone could not induce SFC proliferation, it did however augment IL-1 beta-induced SFC proliferation in a dose-dependent manner, but not tumour necrosis factor alpha-, platelet-derived growth factor-AB- or b-fibroblast growth factor-induced proliferation. This augmentation was completely neutralized by the addition of anti-IL-6 or anti-sIL-6R antibodies. This may be explained by the fact that an amount of IL-6 sufficient to induce SFC proliferation in the presence of sIL-6R was found to be detectable in the IL-1 beta-stimulated-culture supernatant. This evidence suggests that IL-6 is very likely to be involved in synovial cell proliferation in the synovium of RA patients in co-operation with sIL-6R.