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Rheumatology 1999; 38: 1088-1093
© 1999 British Society for Rheumatology

Apocynin, a plant-derived, cartilage-saving drug, might be useful in the treatment of rheumatoid arthritis

F. P. J. G. Lafeber, C. J. Beukelman1, E. van den Worm1, J. L. A. M. van Roy, M. E. Vianen, J. A. G. van Roon, H. van Dijk1 and J. W. J. Bijlsma

Department of Rheumatology and Clinical Immunology, University Medical Centre Utrecht, PO Box 85500, 3508 GA Utrecht and
1 Department of Medicinal Chemistry, Faculty of Pharmacy, Utrecht University, The Netherlands

Correspondence to: F. P. J. G. Lafeber, Department of Rheumatology and Clinical Immunology (F02.127), University Medical Centre Utrecht, PO Box 85500, 3508 GA Urecht, The Netherlands.

Objective. To investigate whether apocynin, 1-(4-hydroxy-3-methoxyphenyl)ethanone, is able to diminish inflammation-induced cartilage destruction in rheumatoid arthritis (RA), studied in a human in vitro model.

Methods. Apocynin was added to cultures of RA peripheral blood mononuclear cells (PBMNC). Cartilage-destructive activity was determined by addition of culture supernatant to tissue samples of human articular cartilage. In addition, the proliferation of PBMNC, their production of tumour necrosis factor alpha (TN-F{alpha}), interleukin (IL)-1 and IL-10, and T-cell production of interferon gamma (IFN-{gamma}) and IL-4, as measures for T1 and T2 cell activity, were determined.

Results. Apocynin was able to counteract RA PBMNC-induced inhibition of cartilage matrix proteoglycan synthesis, while no effect on inflammation-enhanced proteoglycan release was found. The effect was accompanied by a decrease in IL-1 and TNF-{alpha} production by the MNC. No effect on T-cell proliferation was found, but the production of IFN-{gamma}, IL-4 and T-cell-derived IL-10 was strongly diminished. Most important, apocynin did not show any direct adverse effects on chondrocyte metabolism; on the contrary, it diminished the release of proteoglycans from the cartilage matrix.

Conclusion. Apocynin in vitro inhibits inflammation-mediated cartilage destruction without having adverse effects on cartilage. The latter may be an advantage of apocynin over many other non-steroidal anti-inflammatory drugs. Therefore, apocynin might have an added beneficial effect in protecting RA patients from joint destruction.

KEY WORDS: Apocynin, Rheumatoid arthritis, Non-steroidal anti-inflammatory drugs, Cartilage


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