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Effect of inhibitors of eicosanoid metabolism in murine collagen-induced arthritis.

Abstract
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 anti-arthritic agents.
AuthorsD E Griswold, L M Hillegass, P C Meunier, M J DiMartino, N Hanna
JournalArthritis and rheumatism (Arthritis Rheum) Vol. 31 Issue 11 Pg. 1406-12 (Nov 1988) ISSN: 0004-3591 [Print] United States
PMID3142488 (Publication Type: Journal Article)
Chemical References
  • Arachidonic Acids
  • Imidazoles
  • Pyrazoles
  • Serum Amyloid P-Component
  • Thiazoles
  • SK&F 104351
  • Arachidonic Acid
  • Dexamethasone
  • Collagen
  • 6-(4-fluorophenyl)-2,3-dihydro-5-(4-pyridinyl)imidazo(2,1-b)thiazole
  • phenidone
  • Ibuprofen
Topics
  • Animals
  • Arachidonic Acid
  • Arachidonic Acids (antagonists & inhibitors, metabolism)
  • Arthritis (blood, chemically induced, physiopathology)
  • Collagen (pharmacology)
  • Dexamethasone (pharmacology)
  • Ibuprofen (pharmacology)
  • Imidazoles (pharmacology)
  • Male
  • Mice
  • Mice, Inbred DBA
  • Pyrazoles (pharmacology)
  • Serum Amyloid P-Component (blood)
  • Thiazoles (pharmacology)

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