Aurothiomalate and hydroxychloroquine inhibit nitric oxide production in chondrocytes and in human osteoarthritic cartilage.
OBJECTIVE
Nitric oxide (NO) is a destructive mediator produced by activated chondrocytes. The aim of the present study was to investigate the effect of disease-modifying anti-rheumatic drugs (DMARDs) on interleukin-1beta (IL-1beta)-induced NO production in chondrocyte cultures, and in human osteoarthritic cartilage.


RESULTS
Aurothiomalate, hydroxychloroquine, methotrexate and leflunomide inhibited IL-1beta-induced inducible NO synthase (iNOS) expression and NO production in immortalized H4 chondrocytes, while penicillamine and sulfasalazine had no effect. This can be explained by the fact that the four effective DMARDs also suppressed IL-1beta-induced activation of nuclear factor kappa B (NF-kappaB), which is a crucial transcription factor for iNOS. Aurothiomalate and hydroxychloroquine also inhibited IL-1beta-induced NO production in OA cartilage whereas methotrexate and leflunomide had no effect.


CONCLUSIONS
Aurothiomalate and hydroxychloroquine suppressed IL-1beta-induced NO production in chondrocyte cultures and in OA cartilage. The results suggest an additional anti-inflammatory mechanism for aurothiomalate and hydroxychloroquine and indicates their possible therapeutic value in the treatment of osteoarthritis (OA).
Vuolteenaho
K
K
The Immunopharmacological Research Group, Medical School, University of Tampere, Tampere University Hospital, Finland.
Kujala
P
P
Moilanen
T
T
Moilanen
E
E
D000704:Analysis of Variance; D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D006052:Gold Sodium Thiomalate / Q000494:pharmacology*; D006801:Humans; D006886:Hydroxychloroquine / Q000494:pharmacology*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D020370:Osteoarthritis, Knee / Q000188:drug therapy; D012333:RNA, Messenger / Q000032:analysis
D018501:Antirheumatic Agents; D012333:RNA, Messenger; D006052:Gold Sodium Thiomalate; D009569:Nitric Oxide; D006886:Hydroxychloroquine; D052247:Nitric Oxide Synthase Type II