A novel cyclo-oxygenase-2 inhibitor modulates catabolic and antiinflammatory mediators in osteoarthritis

ITB (6-(p-bromophenyl)amino-7-(p-chlorophenyl)indazolo[2',3':1,5]-1,2,4-triazolo[4,3-a]-1,3,5-benzotriazepine) is a novel inhibitor of cyclo-oxygenase-2 (COX-2) with anti inflammatory activity in animal models. In the present study, we investigated the effect of this compound on the production of catabolic or anti inflammatory mediators in osteoarthritis (OA) cartilage. In OA cartilage explants, ITB inhibited the production of prostaglandin E-2 (PGE(2)), tumour necrosis factor-alpha (TNF-alpha) and matrix metalloproteinase-13 (MMP-13) in a concentration-dependent manner, whereas nitrite was partially reduced. On the contrary, ITB increased the production of interleukin (IL)-10 and the expression of heme oxygenase-1 (HO-4). ITB inhibited the production of catabolic mediators at concentrations able to increase IL-10 and HO-1 in OA cartilage, suggesting that this compound may be useful in the prevention of cartilage degradation. (C) 2004 Elsevier Inc. All rights reserved.