Modulation of the effects of interleukin‐1 on glycosaminoglycan synthesis by the urine‐derived interleukin‐1 inhibitor, but not by interleukin‐6

Abstract

Interleukin-1 (IL-1) has been shown to regulate glycosaminoglycan (GAG) synthesis. We therefore investigated whether an IL-1 inhibitor or IL-6 modulates IL-1 biologic activities in human synovial cells and cultured articular cartilage. We found that in the presence of a constant amount of IL-lP, stimulation of hyaluronic acid (HA) synthesis by the IL-1 inhibitor was inhibited in a dose-dependent manner. Similarly, the decrease in sulfated GAG synthesis induced by IL-1 was reversed by the addition of the IL-1 inhibitor. In contrast, IL-6 did not affect the production of HA, prostaglandin E2, or collagenase in synovial cells, nor did it affect GAG in organ cultures when tested in the presence or absence of IL-lP. Hence, IL-6 was ineffective in modulating IL-1 bioactivities on HA or sulfated GAG synthesis. These results emphasize the importance of IL-1 and IL-1 inhibitor in connective tissue destruction

Proinflammatory activity of TWEAK on human dermal fibroblasts and synoviocytes: blocking and enhancing effects of anti-TWEAK monoclonal antibodies

“…Synoviocytes are exquisitely sensitive to mediators of inflammation, such as TNF and IL-1β, and react strongly to direct contact with inflammatory T cells [1,2,3,4,5,6,35]. They are able to secrete numerous proinflammatory molecules, such as PGE 2 , chemokines (i.e.…”

Ciliary neurotrophic factor is an endogenous pyrogen.

“…CNTFRa has a limited tissue distribution and has been found only in neural, muscular, and hepatic tissues (35,36). reported that IL-6 does not induce PGE2 in peripheral tissues (37)(38)(39). Nevertheless, the pyrogenicity of CNTF was blocked by indomethacin, suggesting that CNTF-like IL-1, TNF, IFN, and IL-6-causes fever by inducing the synthesis of prostaglandins.…”

The pivotal role of interleukin-1 in the clinical manifestations of rheumatoid arthritis

“…When compared on a molar basis in this system, the inhibition by IL-1 was much stronger than that afforded by TNFα (which had a very small effect) and interferon-γ (which had no effect at all). Of importance, the inhibitory effect of IL-1 on this repair process was restored when IL-1Ra was added at adequate concentrations [29].…”