The in-vitro effects of avocado and soybean unsaponifiable residues on neutral metalloproteinase activity, cytokines and prostaglandin E-2 (PGE(2)) production by human articular chondrocytes were investigated. Avocado and soybean unsaponifiable residues were mixed in three ratios: 1:2 (A1S2), 2:1 (A2S1) or 1:1 (A2S2). Freshly isolated human chondrocytes were cultured for 72 h in the absence or presence of interleukin-1 beta (IL-1 beta) (17 ng/ml), with or without unsaponifiable residue mixtures at a concentration of 10 mu g/ml. A/S unsaponifiable residues were also tested separately at concentrations of 3.3, 6.6 and 10 mu g/ml. All A/S unsaponifiable mixtures reduced the spontaneous production of stromelysin, interleukin-6 (IL-6), interleukin-8 (IL-8) and prostaglandin E-2 (PGE(2)) by chrondrocytes. At concentrations of 3.3 and 6.6 mu g/ml, A/S residues, tested separately, were potent inhibitors of the production of IL-8 and PGE(2). Nevertheless, only avocado residue inhibited IL-6 production at these concentrations. AIS unsaponifiable mixtures had a more pronounced inhibitory effect on cytokine production than avocado or soybean residues added alone. As anticipated, IL-1 beta induced a marked release of collagenase, stromelysin, IL-6, IL-8 and PGE(2). A/S unsaponifiable mixtures partially reversed the IL-1 effects on chrondrocytes. These findings suggest a potential role for A/S unsaponifiable extracts in mitigating the deleterious effects of IL-1 beta on cartilage.
