Osteoarthritis is characterized by inflammation and increased production of pro-inflammatory mediators including cytokines and prostaglandin E2 (PGE2). Macrophage-like cells in synovial tissue produce these mediators which induce degradative enzymes that break down cartilage. We determined whether avocado/soybean unsaponifiables (ASU) and chondroitin sulfate (CS) can inhibit cytokine expression and PGE2 production using monocyte/macrophage-like cell models. Cells were incubated for 24 hours with either control media alone, ASU alone (NMX1000; 8.3 ?g/ml), CS alone (TRH122; 20 ?g/ml), or a combination of both preparations. Cells were activated with cytokines or lipopolysaccharide for 1 or 24 hours to determine cytokine gene expression by RT-PCR and PGE2 production by immunoassay, respectively. In response to activation, THP-1 cells exhibited increased expression of TNF-? and IL-1?, while RAW cells increased synthesis of PGE2. Cytokine expression and PGE2 synthesis were significantly decreased by the combination of ASU and CS compared to the individual treatments alone (P<0.05). Our finding supports the potential of the ASU and CS combination to suppress the synthesis of pro-inflammatory mediators in the joint.