THE EFFECTS OF CYCLOOXYGENASE-2 INHIBITORS ON CARTILAGE EROSION AND BONE LOSS IN A MODEL OF MYCOBACTERIUM TUBERCULOSIS-INDUCED MONOARTICULAR ARTHRITIS IN THE RAT

Selective cyclooxygenase 2 (COX 2) inhibitors NS-398 and nimesulide we re investigated for their effects on patellar cartilage and bone conte nt in a model of Mycobacterium tuberculosis (M.tb)-induced monoarticul ar arthritis in the rat. The protective/destructive properties of thes e nonsteroidal antiinflammatory drugs (NSAIDs) were compared with piro xicam, known to accelerate cartilage breakdown and reduce bone erosion in this model in comparison to untreated arthritic controls. Male CFH B Wistar rats were injected intraarticularly with heat killed M.tb int o the left stifle joint, resulting in loss of patellar cartilage glyco saminoglycans (GAG), bone erosion and inflammation. The right stifle j oint received saline. Animals were dosed daily, p.o. with NS-398 (1, 1 0 mg/kg), nimesulide (0.5, 5 mg/kg) or piroxicam (10 mg/kg). Four days after M.tb injection, patellar GAG content, bone weight and joint swe lling were measured in drug-treated animals and untreated arthritic co ntrols. Changes in the left joint were compared to the right. The expr ession and distribution of COX 2 protein was determined by immunocytoc hemistry in synovial tissue from arthritic controls over the time cour se. Focal accumulations of inflammatory cells were positively immunola belled for COX 2 in the synovium from the left stifle joint of untreat ed arthritic animals, 6 h after injection of M.tb. Labeling of inflamm atory cell infiltrates increased and was widespread in the synovium at 24 h. By day 4 fibroblasts were positively labelled for COX 2 in addi tion to polymorphonuclear and mononuclear leukocytes. Piroxicam and ni mesulide at the higher dose significantly exacerbated M.tb-induced car tilage GAG loss while NS-398 was without effect. Both COX 2 inhibitors did not alter M.tb-induced patellar bone loss. In contrast, piroxicam significantly reduced bone loss. All COX inhibitors significantly red uced joint swelling. In conclusion, the selective inhibition of COX 2 may result in the amelioration of synovitis with a lowered risk of NSA ID-induced cartilage damage in rheumatic disease.