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THE SYNOVIAL PROSTAGLANDIN SYSTEM IN CHRONIC INFLAMMATORY ARTHRITIS: DIFFERENTIAL EFFECTS OF STEROIDAL AND NONSTEROIDAL ANTI‐INFLAMMATORY DRUGS
Author(s) -
BOMBARDIERI S.,
CATTANI P.,
CIABATTONI G.,
MUNNO O.,
PASERO G.,
PATRONO C.,
PINCA E.,
PUGLIESE F.
Publication year - 1981
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1981.tb08743.x
Subject(s) - thromboxane , prostaglandin , prostaglandin e , medicine , endocrinology , chemistry , arachidonic acid , thromboxane a2 , thromboxane b2 , pharmacology , arthritis , cyclooxygenase , radioimmunoassay , rheumatoid arthritis , eicosanoid , biochemistry , receptor , enzyme , platelet
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 6α‐methyl‐prednisolone (6‐MeP: 4–8mg/day) or indoprofen (1.2g/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 1α and PGF 2α 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 1α 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 1α concentrations were reduced by 35%, PGF 2α 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.