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Logo of annrheumdAnnals of the Rheumatic DiseasesCurrent TOCInstructions for authors
Ann Rheum Dis. Jun 2001; 60(6): 627–631.
PMCID: PMC1753663

Raised levels of F2-isoprostanes and prostaglandin F in different rheumatic diseases


OBJECTIVE—To evaluate oxidative injury and inflammatory status in various rheumatic diseases by measuring the levels of isoprostanes and prostaglandins in serum and synovial fluid.
METHODS—The concentrations of 8-iso-PGF (F2-isoprostane indicating oxidative injury) and 15-keto-dihydro-PGF (a major metabolite of prostaglandin F) were measured in both serum and synovial fluid aspirated from 26 patients with various arthritic diseases, including rheumatoid arthritis (RA), reactive arthritis (ReA), psoriatic arthritis (PsA), and osteoarthritis (OA). These prostaglandin derivatives were also measured in serum samples collected from 42 healthy control subjects.
RESULTS—Overall, serum levels of 8-iso-PGF and 15-keto-dihydro-PGF were much higher in patients with arthritic diseases than in the healthy control subjects. The levels of 8-iso-PGF and 15-keto-dihydro-PGF in synovial fluid aspirated from knee joints were also high and varied among various types of arthritic patients. Although the synovial fluid level of these prostaglandin derivatives was sometimes higher than in the corresponding serum sample, this was not a consistent finding. Overall, there was no correlation between serum and synovial fluid levels of 8-iso-PGF, or between serum and synovial fluid levels of 15-keto-dihydro-PGF. However, a strong relation was found between the levels of 8-iso-PGF and 15-keto-dihydro-PGF2α, in both serum (rs=0.53, p<0.001) and synovial fluid (rs=0.62, p<0.001).
CONCLUSIONS—These data suggest that both free radical mediated oxidative injury and cyclo-oxygenase dependent inflammatory responses are closely correlated in various types of arthritis.

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Selected References

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  • Halliwell B. Oxygen radicals, nitric oxide and human inflammatory joint disease. Ann Rheum Dis. 1995 Jun;54(6):505–510. [PMC free article] [PubMed]
  • Kaur H, Edmonds SE, Blake DR, Halliwell B. Hydroxyl radical generation by rheumatoid blood and knee joint synovial fluid. Ann Rheum Dis. 1996 Dec;55(12):915–920. [PMC free article] [PubMed]
  • Robinson J, Watson F, Bucknall RC, Edwards SW. Activation of neutrophil reactive-oxidant production by synovial fluid from patients with inflammatory joint disease. Soluble and insoluble immunoglobulin aggregates activate different pathways in primed and unprimed cells. Biochem J. 1992 Sep 1;286(Pt 2):345–351. [PMC free article] [PubMed]
  • Stevens CR, Benboubetra M, Harrison R, Sahinoglu T, Smith EC, Blake DR. Localisation of xanthine oxidase to synovial endothelium. Ann Rheum Dis. 1991 Nov;50(11):760–762. [PMC free article] [PubMed]
  • Blake DR, Merry P, Unsworth J, Kidd BL, Outhwaite JM, Ballard R, Morris CJ, Gray L, Lunec J. Hypoxic-reperfusion injury in the inflamed human joint. Lancet. 1989 Feb 11;1(8633):289–293. [PubMed]
  • Humad S, Zarling E, Clapper M, Skosey JL. Breath pentane excretion as a marker of disease activity in rheumatoid arthritis. Free Radic Res Commun. 1988;5(2):101–106. [PubMed]
  • Rowley D, Gutteridge JM, Blake D, Farr M, Halliwell B. Lipid peroxidation in rheumatoid arthritis: thiobarbituric acid-reactive material and catalytic iron salts in synovial fluid from rheumatoid patients. Clin Sci (Lond) 1984 Jun;66(6):691–695. [PubMed]
  • Gutteridge JM, Halliwell B. The measurement and mechanism of lipid peroxidation in biological systems. Trends Biochem Sci. 1990 Apr;15(4):129–135. [PubMed]
  • Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ., 2nd A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9383–9387. [PMC free article] [PubMed]
  • Morrow JD, Awad JA, Kato T, Takahashi K, Badr KF, Roberts LJ, 2nd, Burk RF. Formation of novel non-cyclooxygenase-derived prostanoids (F2-isoprostanes) in carbon tetrachloride hepatotoxicity. An animal model of lipid peroxidation. J Clin Invest. 1992 Dec;90(6):2502–2507. [PMC free article] [PubMed]
  • Reilly M, Delanty N, Lawson JA, FitzGerald GA. Modulation of oxidant stress in vivo in chronic cigarette smokers. Circulation. 1996 Jul 1;94(1):19–25. [PubMed]
  • Morrow JD, Roberts LJ., 2nd The isoprostanes. Current knowledge and directions for future research. Biochem Pharmacol. 1996 Jan 12;51(1):1–9. [PubMed]
  • Basu S, Eriksson M. Oxidative injury and survival during endotoxemia. FEBS Lett. 1998 Nov 6;438(3):159–160. [PubMed]
  • Basu S. Oxidative injury induced cyclooxygenase activation in experimental hepatotoxicity. Biochem Biophys Res Commun. 1999 Jan 27;254(3):764–767. [PubMed]
  • Basu S, Nozari A, Liu XL, Rubertsson S, Wiklund L. Development of a novel biomarker of free radical damage in reperfusion injury after cardiac arrest. FEBS Lett. 2000 Mar 17;470(1):1–6. [PubMed]
  • Meagher EA, Barry OP, Burke A, Lucey MR, Lawson JA, Rokach J, FitzGerald GA. Alcohol-induced generation of lipid peroxidation products in humans. J Clin Invest. 1999 Sep;104(6):805–813. [PMC free article] [PubMed]
  • Basu S, Eriksson M. Lipid peroxidation induced by an early inflammatory response in endotoxaemia. Acta Anaesthesiol Scand. 2000 Jan;44(1):17–23. [PubMed]
  • Fu JY, Masferrer JL, Seibert K, Raz A, Needleman P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes. J Biol Chem. 1990 Oct 5;265(28):16737–16740. [PubMed]
  • Vane JR, Botting RM. A better understanding of anti-inflammatory drugs based on isoforms of cyclooxygenase (COX-1 and COX-2). Adv Prostaglandin Thromboxane Leukot Res. 1995;23:41–48. [PubMed]
  • Xie WL, Chipman JG, Robertson DL, Erikson RL, Simmons DL. Expression of a mitogen-responsive gene encoding prostaglandin synthase is regulated by mRNA splicing. Proc Natl Acad Sci U S A. 1991 Apr 1;88(7):2692–2696. [PMC free article] [PubMed]
  • Basu S. Radioimmunoassay of 15-keto-13,14-dihydro-prostaglandin F2alpha: an index for inflammation via cyclooxygenase catalysed lipid peroxidation. Prostaglandins Leukot Essent Fatty Acids. 1998 May;58(5):347–352. [PubMed]
  • Basu S. Radioimmunoassay of 8-iso-prostaglandin F2alpha: an index for oxidative injury via free radical catalysed lipid peroxidation. Prostaglandins Leukot Essent Fatty Acids. 1998 Apr;58(4):319–325. [PubMed]
  • Ames PR, Alves J, Murat I, Isenberg DA, Nourooz-Zadeh J. Oxidative stress in systemic lupus erythematosus and allied conditions with vascular involvement. Rheumatology (Oxford) 1999 Jun;38(6):529–534. [PubMed]
  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [PubMed]
  • Hirakata M, Suwa A, Takeda Y, Matsuoka Y, Irimajiri S, Targoff IN, Hardin JA, Craft J. Autoantibodies to glycyl-transfer RNA synthetase in myositis. Association with dermatomyositis and immunologic heterogeneity. Arthritis Rheum. 1996 Jan;39(1):146–151. [PubMed]
  • Evans PJ, Cecchini R, Halliwell B. Oxidative damage to lipids and alpha 1-antiproteinase by phenylbutazone in the presence of haem proteins: protection by ascorbic acid. Biochem Pharmacol. 1992 Sep 1;44(5):981–984. [PubMed]
  • Gutteridge JM. Bleomycin-detectable iron in knee-joint synovial fluid from arthritic patients and its relationship to the extracellular antioxidant activities of caeruloplasmin, transferrin and lactoferrin. Biochem J. 1987 Jul 15;245(2):415–421. [PMC free article] [PubMed]

Figures and Tables

Figure 1
Schematic diagram of relation between inflammation and oxidative injury, and endogenous formation of 8-iso-PGF through free radical and 15-keto-dihydro-PGF via cyclo-oxygenase catalysed oxidation of arachidonic acid. ROS = reactive ...
Figure 2
Serum levels of (A) 8-iso-PGF and (B) 15-keto-dihydro-PGF in individual patients with various types of rheumatic disease, and controls. The mean level is represented by a bar in each group.
Figure 3
Synovial fluid levels of (A) 8-iso-PGF and (B) 15-keto-dihydro-PGF in individual patients with various types of rheumatic disease, and controls. The mean level is represented by a bar in each group.

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