thromboxane-b2 and Arthritis--Juvenile

Endogenous synthesis of cysteinyl leukotrienes in juvenile rheumatoid arthritis (JRA) was investigated.. Cysteinyl leukotriene synthesis was assessed by measuring the excretion of leukotriene E4 (LTE4) in urine by radioimmunoassay. The identity of urinary LTE4 was investigated by gas chromatography-mass spectrometry (GC-MS), and 2,3-dinor-thromboxane B2 was measured with GC-MS.. Excretion of LTE4 into urine was significantly (P < 0.05) enhanced in children with JRA compared with that in healthy children (n = 10). Aspirin, in a dosage of 2.5 gm/day, had no effect on urinary LTE4 levels, but it reduced urinary 2,3-dinorthromboxane B2 levels by more than 85% in healthy adults. There was a positive correlation between LTE4 excretion and the number of affected joints.. This study demonstrates a markedly enhanced cysteinyl leukotriene synthesis and a positive correlation between LTE4 excretion and the number of affected joints in children with JRA.

Topics: Adolescent; Adult; Arthritis, Juvenile; Aspirin; Child; Gas Chromatography-Mass Spectrometry; Humans; Leukotriene C4; Leukotriene D4; Leukotriene E4; Thromboxane B2

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.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Aged; Arthritis, Juvenile; Arthritis, Rheumatoid; Female; Humans; Indoprofen; Male; Methylprednisolone; Middle Aged; Phenylpropionates; Prostaglandins; Prostaglandins E; Prostaglandins F; Synovial Fluid; Thromboxane B2; Thromboxanes