The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal anti-inflammatory drugs.
1 The present study was undertaken to characterize the spectrum of arachidonic acid metabolites present in synovial effusions of patients with rheumatoid or psoriatic arthritis, and to compare changes in their concentration following a short-term treatment with 6alpha-methyl-prednisolone (6-MeP: 4-8 mg/day) or indoprofen (1.2 g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect.2 Measurements of prostaglandin E(2) (PGE(2)), thromboxane (TX) B(2), 6-keto-PGF(1alpha) and PGF(2alpha) were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity.3 PGE(2) and TXB(2) accounted for more than 60% of the total immunoreactivity in untreated patients. The absence of any constant ratio between the different arachidonic acid metabolites detected in synovial fluid is consistent with a heterogeneous cellular origin of these compounds.4 Indoprofen treatment was associated with a consistent reduction of synovial prostaglandin and thromboxane concentrations, ranging from 36% in the case of 6-keto-PGF(1alpha) to 90% in the case of PGE(2).5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF(1alpha) concentrations were reduced by 35%, PGF(2alpha) concentrations were increased by 30%, while PGE(2) and TXB(2) were unchanged following 6-MeP.6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE(2) and TXB(2) levels are uncertain, the results of the present study clearly indicate that therapeutic doses of steroidal and nonsteroidal anti-inflammatory drugs cause quite distinct changes in arachidonic acid metabolism, which might be relevant to their specific therapeutic actions and side-effects.
D015121:6-Ketoprostaglandin F1 alpha / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000368:Aged; D001171:Arthritis, Juvenile / Q000188:drug therapy* / Q000378:metabolism; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007216:Indoprofen / Q000627:therapeutic use*; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D010666:Phenylpropionates / Q000627:therapeutic use*; D011453:Prostaglandins / Q000378:metabolism*; D011458:Prostaglandins E / Q000378:metabolism; D011460:Prostaglandins F / Q000378:metabolism; D013582:Synovial Fluid / Q000378:metabolism*; D013929:Thromboxane B2 / Q000378:metabolism*; D013931:Thromboxanes / Q000378:metabolism*
D010666:Phenylpropionates; D011453:Prostaglandins; D011458:Prostaglandins E; D011460:Prostaglandins F; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D007216:Indoprofen; D008775:Methylprednisolone