Margalit A, Duffin K L, Shaffer A F, Gregory S A, Isakson P C
Department of Inflammatory Diseases, Searle Research and Development, St. Louis, Missouri 63198, USA.
Inflammation. 1997 Apr;21(2):205-22. doi: 10.1023/a:1027322304880.
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.
痛风是一种急性风湿性疾病，与单钠尿酸盐（MSU）晶体在关节中的沉积有关。这种疾病的特征是严重疼痛和炎症性关节肿胀的间歇性发作，这些症状似乎是由前列腺素驱动的。在本研究中，我们调查了MSU晶体对小鼠花生四烯酸（AA）代谢的影响。我们已经证明，在注射MSU晶体后，前列腺素和其他AA代谢产物会短暂形成，在10分钟后达到峰值水平。相比之下，在注射MSU晶体后，游离AA水平在2-4小时内保持较高。相比之下，当给予外源性AA而不是MSU晶体时，类花生酸和AA都以相同的高速率减少。用MSU晶体预处理可抑制外源性给予的AA向类花生酸的代谢。当用AA本身、钙离子载体（A23187）或酵母聚糖预处理小鼠时，未观察到AA代谢受到抑制。我们得出结论，对小鼠进行MSU晶体处理会导致短暂的类花生酸产生，随后AA代谢减弱。可能是MSU晶体在痛风中同样抑制AA代谢，从而限制痛风发作的持续时间。
