ABSTRACT
OBJECTIVE: Recent in vitro studies showed that celecoxib, a selective cyclooxygenase (COX)-2 inhibitor, protects human osteoarthritic cartilage tissue from degeneration. The objective was to substantiate these beneficial effects in an in vivo (clinical) study with celecoxib treatment of patients with severe knee osteoarthritis (OA) and subsequent evaluation of cartilage tissue ex vivo. METHODS: Patients with knee OA were treated 4 weeks prior to total knee replacement surgery with either celecoxib 200mg b.d., indomethacin 50mg b.d., or received no treatment. During surgery cartilage and synovium were collected and analyzed in detail ex vivo. RESULTS: When compared to non-treated patients, patients treated with celecoxib showed significant beneficial effects on proteoglycan synthesis, -release, and -content, confirming the in vitro data. In the indomethacin group, no significant differences were found compared to the control group. On the contrary, a tendency towards a lower content and lower synthesis rate was found. In the treated groups prostaglandin-E(2) levels were lower than in the control group, indicating COX-2 inhibition. Ex vivo release of interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha by synovial tissue was decreased by treatment with celecoxib, whereas in the indomethacin group only IL-1 beta release was decreased. CONCLUSION: Using this novel approach we were able to demonstrate an in vivo generated chondrobeneficial effect of celecoxib in patients with end stage knee OA.
Subject(s)
Cartilage, Articular/drug effects , Cyclooxygenase 2 Inhibitors/therapeutic use , Osteoarthritis, Knee/drug therapy , Aged , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Arthroplasty, Replacement, Knee , Cartilage, Articular/metabolism , Cartilage, Articular/pathology , Celecoxib , Dinoprostone/biosynthesis , Female , Humans , Indomethacin/therapeutic use , Interleukin-1beta/metabolism , Male , Matrix Metalloproteinases/metabolism , Middle Aged , Nitric Oxide/biosynthesis , Osteoarthritis, Knee/metabolism , Osteoarthritis, Knee/pathology , Osteoarthritis, Knee/surgery , Proteoglycans/metabolism , Pyrazoles/therapeutic use , Sulfonamides/therapeutic use , Synovial Membrane/drug effects , Synovial Membrane/metabolism , Tumor Necrosis Factor-alpha/metabolismABSTRACT
In several animal models of rheumatoid arthritis (RA), T cell responses to self 60-kD heat-shock protein 60 (hsp60) protect against the induction of arthritis. The nature of this suppressive T cell activity induced by self hsp60 is not clear. In the present study, T cell responses to human (self) hsp60 in RA in terms of type 1 (T1) and type 2 (T2) T cell activity were assessed. The results show that human and not bacterial hsp60-reactive synovial fluid (SF) T cells of patients with RA proliferate in the presence of the T2 cell growth factor IL-4. SF T cells stimulated with human hsp60 produced significantly lower amounts of IFN-gamma and higher amounts of IL-4 than SF T cells stimulated with bacterial hsp60 (P
