The modulation of intra-articular inflammation, cartilage matrix and bone loss in mono-articular arthritis induced by heat-killed Mycobacterium tuberculosis.
Inflammation models for the assessment of anti-rheumatic drug activity utilize a variety of stimuli and sites. However, the determination of cartilage and bone degradation remains time consuming and problematic. A rapid rat model of Mycobacterium tuberculosis monoarticular arthritis with induces of inflammation, as well as patellar cartilage proteoglycan and bone degradation has been reported. This study characterizes this model with respect to the actions of anti-rheumatic drugs. Dexamethasone, cyclosporin and prednisolone inhibited all three parameters. Methotrexate inhibited joint inflammation alone, whilst azathioprine was without effect. Levamisole inhibited cartilage and bone degradation without affecting joint inflammation. NSAIDs were divided in their actions. Naproxen, piroxicam, diclofenac and tiaprofenic acid all inhibited joint inflammation and bone loss, but naproxen and piroxicam both significantly potentiated cartilage proteoglycan loss. This model appears to rely on cellular recruitment at this early stage, the anti-metabolites being ineffective. The modulation of inflammation can result in a protection against cartilage and bone damage in arthritis; however, certain NSAIDs are detrimental to cartilage integrity. The pharmacological manipulation of inflammatory arthritis can therefore dislocate inflammation from its effects on tissue destruction.
Seed
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MP
Experimental Pathology Group, William Harvey Research Institute, Saint Bartholomew's and Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, Charterhouse Square, London EC1M 6BQ, UK. m.p.seed@qmul.ac.uk
Gardner
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CR
D000818:Animals; D018501:Antirheumatic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D001379:Azathioprine / Q000008:administration & dosage / Q000627:therapeutic use; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000627:therapeutic use; D006025:Glycosaminoglycans / Q000378:metabolism; D006358:Hot Temperature; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D007978:Levamisole / Q000008:administration & dosage / Q000627:therapeutic use; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010014:Osteolysis / Q000378:metabolism / Q000517:prevention & control*; D010080:Oxazoles / Q000008:administration & dosage / Q000627:therapeutic use; D010329:Patella / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology
D018501:Antirheumatic Agents; D006025:Glycosaminoglycans; D007166:Immunosuppressive Agents; D010080:Oxazoles; D007978:Levamisole; D003907:Dexamethasone; D016572:Cyclosporine; D011239:Prednisolone; C063528:romazarit; D001379:Azathioprine