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 disease is characterized by intermittent episodes of severe pain and inflammatory joint swelling which are seemingly driven by prostaglandins. In this study we investigated the effect of MSU crystals on arachidonic acid (AA) metabolism in the mouse. We have demonstrated that prostaglandins and other AA metabolites were transiently formed after MSU crystal injection with peak levels occurring after 10 min. In contrast, free AA levels remained high for 2-4 hours after MSU crystal injection. By contrast, when exogenous AA was administered instead of MSU crystals, both the eicosanoids and AA diminished at the same high rates. The metabolism of exogenously administered AA to eicosanoids was inhibited by pretreatment with MSU crystals. No inhibition of AA metabolism was observed when mice were pretreated with AA itself, Ca2+ ionophore (A23187), or zymosan. We conclude that the MSU crystal treatment of mice results in a transient eicosanoid production which is followed by attenuated AA metabolism. It could be that MSU crystals similarly inhibit AA metabolism in gout and thereby limit the duration of gout attacks.
Margalit
A
A
Department of Inflammatory Diseases, Searle Research and Development, St. Louis, Missouri 63198, USA.
Duffin
K L
KL
Shaffer
A F
AF
Gregory
S A
SA
Isakson
P C
PC
D000818:Animals; D016718:Arachidonic Acid / Q000008:administration & dosage / Q000378:metabolism*; D015210:Arthritis, Gouty / Q000209:etiology / Q000378:metabolism; D003460:Crystallization; D004195:Disease Models, Animal; D015777:Eicosanoids / Q000096:biosynthesis; D005260:Female; D006073:Gout / Q000209:etiology* / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D010529:Peritoneal Cavity; D011453:Prostaglandins / Q000096:biosynthesis; D014527:Uric Acid / Q000008:administration & dosage* / Q000378:metabolism*
D015777:Eicosanoids; D011453:Prostaglandins; D014527:Uric Acid; D016718:Arachidonic Acid