ALTERED ARACHIDONIC-ACID METABOLISM IN URATE CRYSTAL-INDUCED INFLAMMATION

Gout is an acute rheumatic disorder that occurs in connection with the deposition of monosodium urate (MSU) crystals in the joints. This dis ease is characterized by intermittent episodes of severe pain and infl ammatory joint swelling which are seemingly driven by prostaglandins. In this study we investigated the effect of MSU crystals on arachidoni c acid (AA) metabolism in the mouse. We have demonstrated that prostag landins and other AA metabolites were transiently formed after MSU cry stal injection with peak levels occurring after 10 min. In contrast, f ree AA levels remained high for 2-4 hours after MSU crystal injection. By contrast, when exogenous AA was administered instead of MSU crysta ls, both the eicosanoids and AA diminished at the same high rates. The metabolism of exogenously administered AA to eicosanoids was inhibite d by pretreatment with MSU crystals. No inhibition of AA metabolism wa s observed when mice were pretreated with AA itself, Ca2+ ionophore (A 23187), or zymosan. We conclude that the MSU crystal treatment of mice results in a transient eicosanoid production which is followed by att enuated AA metabolism. It could be that MSU crystals similarly inhibit AA metabolism in gout and thereby limit the duration of gout attacks.