Anti-interleukin-1 effects of diacerein and rhein in human osteoarthritic synovial tissue and cartilage cultures

Objective: The etiology of osteoarthritis (OA) is still a matter of debate. Several factors are known to be involved in the destruction of the articul ar cartilage. Interleukin-l (IL-1) plays an important role in the pathogene sis of osteoarthritis (OA) either directly or through the stimulation of ca tabolic factors, such as nitric oxide (NO). The objective of this study was to evaluate the effect of diacerein, a new anti-GA agent and its active me tabolite, rhein, on the production and function of IL-1 beta, nitric oxide (NO) and receptor agonist (IL-1ra) in human OA cartilage and synovial tissu e cultures. Design: Synovial tissue and cartilage derived from OA patients were kept in culture for 48-72 hours in the presence of 1 mu g/ml of lipopolysaccharide (LPS) with or without diacerein (10(-7)-10(-5) M), rhein (10(-7)-10(-5) IC I) and hydrocortisone (5 mu g/ml). IL-1 beta, IL-1ra, NO productions and S- 35 uptake were measured in culture media. In some experiments the resulting supernatants from synovial tissue cultures were added to cartilage. Results: Diacerein and rhein, as well as hydrocortisone, significantly inhi bited LPS-induced IL-1 beta production by synovial tissue and cartilage. Th ey also significantly reversed the inhibitory effect of LPS on cartilage S- 35 uptake. Culture media from synovial tissue containing LPS+diacerein (10( -6) M) or +rhein (10(-6) M) had a significantly less inhibitory effect on c artilage synthesis than culture media containing LPS only. Diacerein and rh ein decreased NO release in synovial tissue and cartilage media and increas ed IL-1ra levels in cartilage culture media. Conclusion: An inhibitory effect of diacerein and rhein at therapeutic conc entrations on both IL-1 beta secretion and function in human synovial tissu e and cartilage is suggested. Diacerein and rhein effects on NO production by LPS-stimulated OA synovial tissue and cartilage may both contribute and elucidate their anti-GA properties.