Skip to main content
Log in

Association between hypoxanthine concentration in synovial fluid and joint destruction in patients with rheumatoid arthritis

  • Original Paper
  • Published:
Japanese Journal of Rheumatology

Abstract

To evaluate the significance of augmented levels of hypoxanthine in synovial fluids in patients with rheumatoid arthritis (RA), the hypoxanthine level in the synovial fluid was investigated in association with joint damage. Concentrations of hypoxanthine, xanthine and uric acid in synovial fluids from knee joints of 45 patients with RA, six patients with gout and five patients with osteoarthritis were determined by high performance liquid chromatography. Relationships between these oxypurines and markers for joint inflammation or Larsen grade of knee joint X-ray film were analyzed. Hypoxanthine levels were significantly elevated in patients with RA and with gout but not in those with osteoarthritis. In RA patients, levels of synovial fluid hypoxanthine were correlated with matrix metalloproteinases MMP-3 (r=0.510), but not with C-reactive protein nor synovial fluid cytokines. Among various biological factors in synovial fluid (including cytokines and metalloproteinases) only hypoxanthine levels were significantly (P<0.05) positively correlated with Larsen’s grade of knee joint. In conclusion, augmented levels of synovial hypoxanthine can indicate joint damage in patients with RA and might be a useful marker in a clinical context.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Cohen MV: Free radicals in ischemic and reperfusion myocardial injury: is this the time for clinical trials?Ann Intern Med 111: 918–931, 1989.

    PubMed  CAS  Google Scholar 

  2. Wikstrom G, Ronquist G, Nilsson Set al.: Continuous monitoring of energy metabolites using microdialysis during myocardial ischaemia in the pig,Eur Heart J 16: 339–347, 1995.

    PubMed  CAS  Google Scholar 

  3. Kennedy TP, Rao NV, Hopkins Cet al.: Role of reactive oxygen species in reperfusion injury of the rabbit lung,J Clin Invest 83: 1326–1335, 1989

    Article  PubMed  CAS  Google Scholar 

  4. Grune T, Mueller R, Jakstadt Met al.: Is hypoxanthine a useful marker of perinatal hypoxia?Adv Exp Med Biol 370: 295–298 1994

    PubMed  CAS  Google Scholar 

  5. Mineo I, Kono N, Shimizu Tet al.: Excess purine degradation in exercising muscles of patients with glycogen storage disease types V and VII.J Clin Invest 76: 556–560 1985.

    Article  PubMed  CAS  Google Scholar 

  6. Yamanaka H, Kawagoe Y, Taniguchi Aet al.: Accelerated purine nucleotide degradation by anaerobic but not aerobic ergometer muscle exercise.Metabolism 41: 364–369, 1992.

    Article  PubMed  CAS  Google Scholar 

  7. Fox IH, Palella TD, Kelley WN: Hyperuricemia: a marker for cell energy crisis.New Engl J Med 317: 111–112, 1987.

    Article  PubMed  CAS  Google Scholar 

  8. Herbert KE, Scott DL, Perrett D: Nucleosides and bases in synovial fluid from patients with rheumatoid arthritis and osteoarthritis.Clin Sci 74: 97–99, 1988.

    PubMed  CAS  Google Scholar 

  9. Gudbjornsson B, Zak A, Niklasson Fet al.: Hypoxanthine, xanthine, and urate in synovial fluid from patients with inflammatory arthritides.Ann Rheum Dis 50: 669–672, 1991.

    Article  PubMed  CAS  Google Scholar 

  10. Arnett FC, Edworthy SM, Bloch DAet al.: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.Arthritis Rheum 31: 315–324, 1988.

    Article  PubMed  CAS  Google Scholar 

  11. Wallece SL, Robinson H, Masi ATet al.: Preliminary criteria for the classification of the acute arthritis of primary gout.Arthritis Rheum 20: 895–900, 1977.

    Article  Google Scholar 

  12. Kojima T, Nishina T, Kitamura Met al.: Biochemical studies on the purine metabolism of four cases with hereditary xanthinuria.Clin Chim Acta 137: 189–198, 1984.

    Article  PubMed  CAS  Google Scholar 

  13. Harigai M, Hara M, Yoshimura Tet al.: Monocyte chemoattractant protein-1 (MCP-1) in inflammatory joint disease and its involvement in the cytokine network of rheumatoid synovium.Clin Immunol Immunopath 69: 83–91, 1993.

    Article  CAS  Google Scholar 

  14. Obata K, Iwata K, Okada Yet al.: A one-step sandwich enzyme immunoassay for human matrix metalloproteinase 3 (stromelysin-1) using monoclonal antibodies.Clin Chim Acta 211: 59–72, 1992.

    Article  PubMed  CAS  Google Scholar 

  15. Kodama S, Iwata K, Iwata Het al.: Rapid one-step sandwich enzyme immunoassay for tissue inhibitor of metalloproteinases. An application for rheumatoid arthritis serum and plasma.J Immunol Methods 127: 103–108, 1990.

    Article  PubMed  CAS  Google Scholar 

  16. Larsen A, Dale K, Eek M: Radiographic evaluation of rheumatoid arthritis and related conditions by standard reference films,Acta Radiologica Diagnosis 18: 481–491, 1997.

    Google Scholar 

  17. Stevens CR, Williams RB, Fared AJet al.: Hypoxia and inflammatory synovitis: observations and speculation.Ann Rheum Dis 50: 124–132, 1991.

    Article  PubMed  CAS  Google Scholar 

  18. Woodruff T, Blake DR, Freeman Jet al.: Is chronic synovitis an example of reperfusion injury?Ann Rheum Dis 45: 608–611, 1987.

    Article  Google Scholar 

  19. Tsuboguchi S, Matsui N, Taneda Yet al.: Arthroscopic findings of cartilage changes in knees with rheumatoid arthritis.Ryumachi 29: 110–117, 1989.

    PubMed  CAS  Google Scholar 

  20. Manicourt DH, Fujimoto N, Obata Ket al.: Levels of circulating collagenase, stromelysin-1, and tissue inhibitor of matrix metalloproteinases 1 in patients with rheumatoid arthritis. Relationship to serum levels of antigenic keratin sulfate and systemic parameters of inflammation.Arthritis Rheum 38: 1031–1039, 1995.

    Article  PubMed  CAS  Google Scholar 

  21. Allen RE, Outhwaite JM, Morris CJet al.: Xanthine oxidoreductase is present in human synovium.Ann Rheum Dis 46: 843–845, 1987.

    Article  PubMed  CAS  Google Scholar 

  22. Stevens CR, Benboubetra M, Harrison Ret al.: Localization of xanthine oxidase to synovial endothelium.Ann Rheum Dis 50: 760–762, 1991.

    Article  PubMed  CAS  Google Scholar 

  23. Saari H, Konttinen YT, Friman Cet al.: Differential effects of reactive oxygen species on native synovial fluid and purified human umbilical cord hyaluronate.Inflammation 17: 403–415, 1993.

    Article  PubMed  CAS  Google Scholar 

  24. Singh D, Nazhat NB, Fairburn Ket al.: Electron spin resonance spectroscopic demonstration of the generation of reactive oxygen species by diseased human synovial tissue following ex vivo hypoxia-reoxygenation.Ann Rheum Dis 54: 94–99, 1995.

    Article  PubMed  CAS  Google Scholar 

  25. Weinblatt ME, Coblyn JS, Fox DAet al.: Efficacy of low dose of methotrexate in rheumatoid arthritis.N Engl J Med 312: 818–822, 1985.

    PubMed  CAS  Google Scholar 

  26. Alt FW, Kellems RE, Bertino JRet al.: Multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells.J Biol Chem 253: 1357–1360, 1978.

    PubMed  CAS  Google Scholar 

  27. Nakajima A, Hakoda M, Yamanaka Het al.: Divergent effects of methotrexate on the clonal growth of T and B lymphocytes and synovial adherent cells from patients with rheumatoid arthritis.Ann Rheum Dis 55: 237–242, 1996.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

About this article

Cite this article

Nakanishi, Y., Yamanaka, H., Hakoda, M. et al. Association between hypoxanthine concentration in synovial fluid and joint destruction in patients with rheumatoid arthritis. Japanese Journal of Rheumatology 8, 59–67 (1998). https://doi.org/10.1007/BF03041309

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03041309

Key words

Navigation