Intra-articular steroid treatment reduces synovial HMGB1 but not IL-1 expression in chronic arthritis

Objective

In this study we examined the effect of glucocorticosteroids (GCs) in chronic arthritis on IL-1α, IL-1β, TNF and the newly discovered proinflammatory cytokine HMGB1, which was previously thought of only as a DNA-binding protein.

Methods

Seventeen chronic inflammatory arthritis patients with swelling and pain in at least one large joint were chosen. Synovial biopsies were sampled by arthroscopy before and 9–12 days after intra-articular injection of 40 mg triamcinolone hexacetonide. Synovial membrane T cells (CD3), macrophages (CD68, CD163), as well as the proinflammatory cytokines IL-1α, IL-1β, TNF and HMGB1 were studied by immunohistochemistry followed by semiquantitative analysis and/or digital image analysis.

Results

All investigated joints had clinical signs of active arthritis with swelling and pain of the joint before treatment, which was reduced in all joints after treatment. Numbers of T cells were reduced whereas numbers of macrophages were not significantly changed. Expression of HMGB1 was significantly reduced, whereas no significant effects were seen on the expression of IL-1α, IL-1β or TNF. Before treatment HMGB1 staining was mainly extracellular and cytoplasmic in the mononuclear inflammatory follicles and lining layer, whereas endothelial cells of scattered capillaries, arterioles and venules had a primarily cytoplasmic staining. After treatment staining pattern was more prominent in the nucleus and reduced extracellularly.

Conclusions

Proinflammatory cytokines in chronic arthritis are affected differently by intra-articular GCs. The marked reduction in HMGB1 expression and the lack of significant change in IL-1 and TNF thus indicate that GCs may exert their in vivo effects in arthritis via partly different pathways than in previous in vitro experiments.