Synovial fluid proteins are required for the induction of interleukin-1β production by monosodium urate crystals.

OBJECTIVES

Monosodium urate (MSU) crystal deposition in gouty joints promotes the release of inflammatory mediators, in particular interleukin (IL)-1β. The induction of IL-1β production by MSU crystals requires a co-stimulus. The objective of this study was to determine which part of the synovial fluid (SF) provides co-stimulation to MSU crystals to induce IL-1β in macrophages.

METHOD

The lipidic fraction (LF) and the protein fraction (PF) were isolated from the SF of patients with arthropathies. The PF was subfractionated according to different molecular weight (MW) ranges. THP-1 cells or human primary monocytes were stimulated with MSU crystals in the presence or absence of SF or SF fractions. IL-1β and IL-8 production and IL-1β mRNA expression were assessed by an enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qPCR).

RESULTS

Exposure of monocytes/macrophages to MSU crystals alone induced the moderate release of IL-8 but not of IL-1β. The production of IL-1β required the presence of both SF from patients with inflammatory arthritis (SFi) and MSU crystals. SF from patients with non-inflammatory arthritis, that is patients with osteoarthritis (OA), did not affect the IL-1β production but slightly enhanced the secretion of IL-8. Both MSU crystals and SFi were required for the induction of the IL-1β transcript, which was not expressed in the presence of either stimulus alone. SFi fractionation demonstrated that the MSU crystal co-stimulus was contained in the PF of SFi with MW > 50 kDa but not in the LF.

CONCLUSIONS

This study shows that the SF of inflammatory arthritis patients, including gout patients, contains proteins required for the induction of IL-1β by MSU crystals in macrophages whereas lipids are not involved.