Effect of inhibitors of eicosanoid metabolism in murine collagen‐induced arthritis

The dual inhibitors of arachidonic acid metabolism, Smith Kline & French (SK&F) 86002, SK&F 104351, and phenidone; the corticosteroid, dexamethasone; and the selective cyclooxygenase inhibitors, ibuprofen, indomethacin, naproxen, and piroxicam were evaluated for their antiarthritic poten...

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Published in:Arthritis and rheumatism 1988-11, Vol.31 (11), p.1406-1412
Main Authors: Griswold, Don E., Hillegass, Leonard M., Meunier, Paul C., Dimartino, Michael J., Hanna, Nabil
Format: Article
Language:English
Subjects:
Animals
Arachidonic Acid
Arachidonic Acids - antagonists & inhibitors
Arachidonic Acids - metabolism
Arthritis - blood
Arthritis - chemically induced
Arthritis - physiopathology
Biological and medical sciences
Collagen - pharmacology
Dexamethasone - pharmacology
Diseases of the osteoarticular system
Ibuprofen - pharmacology
Imidazoles - pharmacology
Inflammatory joint diseases
Male
Medical sciences
Mice
Mice, Inbred DBA
Pyrazoles - pharmacology
Serum Amyloid P-Component - blood
Thiazoles - pharmacology
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Summary:The dual inhibitors of arachidonic acid metabolism, Smith Kline & French (SK&F) 86002, SK&F 104351, and phenidone; the corticosteroid, dexamethasone; and the selective cyclooxygenase inhibitors, ibuprofen, indomethacin, naproxen, and piroxicam were evaluated for their antiarthritic potency in the murine, collagen‐induced arthritis model. The ability of these compounds to alter the severity of arthritic lesions and to reduce serum levels of the acute‐phase reactant, serum amyloid P component (SAP) were monitored. Serum concentrations of SAP were found to correlate strongly (r = 0.985) with disease severity at day 35 postimmunization. Treatment with SK&F 86002, SK&F 104351, phenidone, or dexamethasone significantly reduced disease severity, as judged by clinical score (55%, 72%, 41%, and 45% inhibition, respectively) and SAP levels (62%, 94%, 52%, and 94% inhibition, respectively) in arthritic mice. This profile of activity was not shared by the selective cyclooxygenase inhibitors, which did not uniformly inhibit disease activity by both parameters. The results suggest that dual inhibitors of 5‐lipoxygenase and cyclooxygenase may prove more effective than selective cyclooxygenase inhibitors as antiarthritic agents.
ISSN:0004-3591
1529-0131
DOI:10.1002/art.1780311110