Abstract
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: 4-8 mg/day) or indoprofen (1.2 g/day), a nonsteroidal anti-inflammatory agent with proven synovial prostaglandin inhibitory effect.
2 Measurements of prostaglandin E2 (PGE2), thromboxane (TX) B2, 6-keto-PGF1α and PGF2α were performed by radioimmunoassay techniques in synovial effusions obtained from 23 patients, and validated by thin-layer chromatographic analysis of the extracted immunoreactivity.
3 PGE2 and TXB2 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-PGF1α to 90% in the case of PGE2.
5 In contrast, 6-MeP caused opposite changes on different metabolites originating via the cyclo-oxygenase pathway. Thus, 6-keto-PGF1α concentrations were reduced by 35%, PGF2α concentrations were increased by 30%, while PGE2 and TXB2 were unchanged following 6-MeP.
6 Although the mechanism(s) underlying the failure of 6-MeP to reduce synovial PGE2 and TXB2 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.
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Selected References
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- Atkinson J. P., Frank M. M. Effect of cortisone therapy on serum complement components. J Immunol. 1973 Oct;111(4):1061–1066. [PubMed] [Google Scholar]
- Blackwell G. J., Flower R. J., Nijkamp F. P., Vane J. R. Phospholipase A2 activity of guinea-pig isolated perfused lungs: stimulation, and inhibition by anti-inflammatory steroids. Br J Pharmacol. 1978 Jan;62(1):79–89. doi: 10.1111/j.1476-5381.1978.tb07009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Carnuccio R., Di Rosa M., Persico P. Hydrocortisone-induced inhibitor of prostaglandin biosynthesis in rat leucocytes. Br J Pharmacol. 1980 Jan;68(1):14–16. doi: 10.1111/j.1476-5381.1980.tb10691.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Caruso I., Moro E., Patrono C., Sacchetti G., Tamassia V., Tosolini G. P. Plasma and synovial fluid pharmacokinetics and prostaglandin inhibitory effect of indoprofen in patients with rheumatoid arthritis. Scand J Rheumatol. 1980;9(2):123–126. doi: 10.3109/03009748009098141. [DOI] [PubMed] [Google Scholar]
- Ciabattoni G., Pugliese F., Spaldi M., Cinotti G. A., Patrono C. Radioimmunoassay measurement of prostaglandins E2 and F2alpha in human urine. J Endocrinol Invest. 1979 Apr-Jun;2(2):173–182. doi: 10.1007/BF03349310. [DOI] [PubMed] [Google Scholar]
- Ferreira S. H., Moncada S., Vane J. R. Indomethacin and aspirin abolish prostaglandin release from the spleen. Nat New Biol. 1971 Jun 23;231(25):237–239. doi: 10.1038/newbio231237a0. [DOI] [PubMed] [Google Scholar]
- Flower R. J., Blackwell G. J. Anti-inflammatory steroids induce biosynthesis of a phospholipase A2 inhibitor which prevents prostaglandin generation. Nature. 1979 Mar 29;278(5703):456–459. doi: 10.1038/278456a0. [DOI] [PubMed] [Google Scholar]
- Flower R. J., Blackwell G. J. The importance of phospholipase-A2 in prostaglandin biosynthesis. Biochem Pharmacol. 1976 Feb 1;25(3):285–291. doi: 10.1016/0006-2952(76)90216-1. [DOI] [PubMed] [Google Scholar]
- Herman A. G., Claeys M., Moncada S., Vane J. R. Biosynthesis of prostaglandin (PGI2) and 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE) by pericardium, pleura, peritoneum and aorta of the rabbit. Prostaglandins. 1979 Sep;18(3):439–452. doi: 10.1016/s0090-6980(79)80062-3. [DOI] [PubMed] [Google Scholar]
- Hirata F., Schiffmann E., Venkatasubramanian K., Salomon D., Axelrod J. A phospholipase A2 inhibitory protein in rabbit neutrophils induced by glucocorticoids. Proc Natl Acad Sci U S A. 1980 May;77(5):2533–2536. doi: 10.1073/pnas.77.5.2533. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Humes J. L., Bonney R. J., Pelus L., Dahlgren M. E., Sadowski S. J., Kuehl F. A., Jr, Davies P. Macrophages synthesis and release prostaglandins in response to inflammatory stimuli. Nature. 1977 Sep 8;269(5624):149–151. doi: 10.1038/269149a0. [DOI] [PubMed] [Google Scholar]
- KENT J. F., FIFE E. H., Jr Precise standardization of reagents for complement fixation. Am J Trop Med Hyg. 1963 Jan;12:103–116. doi: 10.4269/ajtmh.1963.12.103. [DOI] [PubMed] [Google Scholar]
- Kinsella T. D., Baum J., Ziff M. Studies of isolated synovial living cells of rheumatoid and nonrheumatoid synovial membranes. Arthritis Rheum. 1970 Nov-Dec;13(6):734–753. doi: 10.1002/art.1780130603. [DOI] [PubMed] [Google Scholar]
- Levine L. Antibodies to pharmacologically active molecules: specificities and some applications of antiprostaglandins. Pharmacol Rev. 1973 Jun;25(2):293–307. [PubMed] [Google Scholar]
- Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
- Morley J., Bray M. A., Jones R. W., Nugteren D. H., van Dorp D. A. Prostaglandin and thromboxane production by human and guinea-pig macrophages and leucocytes. Prostaglandins. 1979 May;17(5):729–746. doi: 10.1016/s0090-6980(79)80044-1. [DOI] [PubMed] [Google Scholar]
- Nijkamp F. P., Flower R. J., Moncada S., Vane J. R. Partial purification of rabbit aorta contracting substance-releasing factor and inhibition of its activity by anti-inflammatory steroids. Nature. 1976 Oct 7;263(5577):479–482. doi: 10.1038/263479a0. [DOI] [PubMed] [Google Scholar]
- Paget S. A., Gibofsky A. Immunopathogenesis of rheumatoid arthritis. Am J Med. 1979 Dec;67(6):961–970. doi: 10.1016/0002-9343(79)90636-3. [DOI] [PubMed] [Google Scholar]
- Patrono C., Ciabattoni G., Pugliese F., Pinca E., Castrucci G., De Salvo A., Satta M. A., Parachini M. Radioimmunoassay of serum thromboxane B2: a simple method of assessing pharmacologic effects on platelet function. Adv Prostaglandin Thromboxane Res. 1980;6:187–191. [PubMed] [Google Scholar]
- ROPES M. W., BENNETT G. A., COBB S., JACOX R., JESSAR R. A. 1958 Revision of diagnostic criteria for rheumatoid arthritis. Bull Rheum Dis. 1958 Dec;9(4):175–176. [PubMed] [Google Scholar]
- Samuelsson B., Borgeat P., Hammarström S., Murphy R. C. Introduction of a nomenclature: leukotrienes. Prostaglandins. 1979 Jun;17(6):785–787. doi: 10.1016/0090-6980(79)90052-2. [DOI] [PubMed] [Google Scholar]
- Smith J. B., Willis A. L. Aspirin selectively inhibits prostaglandin production in human platelets. Nat New Biol. 1971 Jun 23;231(25):235–237. doi: 10.1038/newbio231235a0. [DOI] [PubMed] [Google Scholar]
- Sturge R. A., Yates D. B., Gordon D., Franco M., Paul W., Bray A., Morley J. Prostaglandin production in arthritis. Ann Rheum Dis. 1978 Aug;37(4):315–320. doi: 10.1136/ard.37.4.315. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trang L. E., Granström E., Lövgren O. Levels of prostaglandins F2 alpha and E2 and thromboxane B2 in joint fluid in rheumatoid arthritis. Scand J Rheumatol. 1977;6(3):151–154. doi: 10.3109/03009747709095440. [DOI] [PubMed] [Google Scholar]
- Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
