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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Jan;83(1):52–57. doi: 10.1111/j.1365-2249.1991.tb05587.x

Human cartilage is degraded by rheumatoid arthritis synovial fluid but not by recombinant cytokines in vitro.

A P Hollander 1, R M Atkins 1, D M Eastwood 1, P A Dieppe 1, C J Elson 1
PMCID: PMC1535467  PMID: 1988232

Abstract

Rheumatoid arthritis (RA) synovial fluid (SF) stimulated significant loss of glycosaminoglycans (GAG) from normal and pathological human cartilage biopsies over 2 days as compared with normal human serum. By contrast, 15 RA SFs failed to degrade killed normal cartilage, and degraded killed RA cartilage less effectively than living RA cartilage. Four RA SFs were treated with neutralizing anti-cytokine antisera prior to incubation with normal cartilage. The degrading effects of two of the fluids were reversed by anti-interleukin-1 alpha (IL-1 alpha) while degradation by the third and fourth fluids were reversed by anti-interleukin-1 beta (IL-1 beta) and anti-tumour necrosis factor-alpha (TNF-alpha), respectively. However, recombinant human IL-1 alpha, IL-1 beta, TNF alpha or a combination of all three cytokines had no degrading effect in this 2-day culture system. It is concluded that RA SF degrades cartilage by a mechanism involving a synergistic interaction between cytokines and some other component of SF.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bendtzen K., Petersen J., Halkjaer-Kristensen J., Ingemann-Hansen T. Interleukin-1-like activities in synovial fluids of patients with rheumatoid arthritis and traumatic synovitis. Rheumatol Int. 1985;5(2):79–82. doi: 10.1007/BF00270301. [DOI] [PubMed] [Google Scholar]
  2. Bensouyad A., Hollander A. P., Dularay B., Bedwell A. E., Cooper R. A., Hutton C. W., Dieppe P. A., Elson C. J. Concentrations of glycosaminoglycans in synovial fluids and their relation with immunological and inflammatory mediators in rheumatoid arthritis. Ann Rheum Dis. 1990 May;49(5):301–307. doi: 10.1136/ard.49.5.301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buchan G., Barrett K., Turner M., Chantry D., Maini R. N., Feldmann M. Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 alpha. Clin Exp Immunol. 1988 Sep;73(3):449–455. [PMC free article] [PubMed] [Google Scholar]
  4. Clay K., Seed M. P., Clements-Jewery S. Studies on interleukin-1 beta induced glycosaminoglycan release from rat femoral head cartilage in-vitro. J Pharm Pharmacol. 1989 Jul;41(7):503–504. doi: 10.1111/j.2042-7158.1989.tb06514.x. [DOI] [PubMed] [Google Scholar]
  5. Dean D. D., Martel-Pelletier J., Pelletier J. P., Howell D. S., Woessner J. F., Jr Evidence for metalloproteinase and metalloproteinase inhibitor imbalance in human osteoarthritic cartilage. J Clin Invest. 1989 Aug;84(2):678–685. doi: 10.1172/JCI114215. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dingle J. T., Page Thomas D. P., King B., Bard D. R. In vivo studies of articular tissue damage mediated by catabolin/interleukin 1. Ann Rheum Dis. 1987 Jul;46(7):527–533. doi: 10.1136/ard.46.7.527. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dingle J. T., Saklatvala J., Hembry R., Tyler J., Fell H. B., Jubb R. A cartilage catabolic factor from synovium. Biochem J. 1979 Oct 15;184(1):177–180. doi: 10.1042/bj1840177. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dularay B., Elson C. J., Clements-Jewery S., Damais C., Lando D. Recombinant human interleukin-1 beta primes human polymorphonuclear leukocytes for stimulus-induced myeloperoxidase release. J Leukoc Biol. 1990 Feb;47(2):158–163. doi: 10.1002/jlb.47.2.158. [DOI] [PubMed] [Google Scholar]
  9. Eeckhout Y., Vaes G. Further studies on the activation of procollagenase, the latent precursor of bone collagenase. Effects of lysosomal cathepsin B, plasmin and kallikrein, and spontaneous activation. Biochem J. 1977 Jul 15;166(1):21–31. doi: 10.1042/bj1660021. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Farndale R. W., Buttle D. J., Barrett A. J. Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue. Biochim Biophys Acta. 1986 Sep 4;883(2):173–177. doi: 10.1016/0304-4165(86)90306-5. [DOI] [PubMed] [Google Scholar]
  11. Farndale R. W., Sayers C. A., Barrett A. J. A direct spectrophotometric microassay for sulfated glycosaminoglycans in cartilage cultures. Connect Tissue Res. 1982;9(4):247–248. doi: 10.3109/03008208209160269. [DOI] [PubMed] [Google Scholar]
  12. Fontana A., Hengartner H., Weber E., Fehr K., Grob P. J., Cohen G. Interleukin 1 activity in the synovial fluid of patients with rheumatoid arthritis. Rheumatol Int. 1982;2(2):49–53. doi: 10.1007/BF00541245. [DOI] [PubMed] [Google Scholar]
  13. Henderson B., Pettipher E. R. Arthritogenic actions of recombinant IL-1 and tumour necrosis factor alpha in the rabbit: evidence for synergistic interactions between cytokines in vivo. Clin Exp Immunol. 1989 Feb;75(2):306–310. [PMC free article] [PubMed] [Google Scholar]
  14. Henderson B., Pettipher E. R. Comparison of the in vivo inflammatory activities after intra-articular injection of natural and recombinant IL-1 alpha and IL-1 beta in the rabbit. Biochem Pharmacol. 1988 Nov 1;37(21):4171–4176. doi: 10.1016/0006-2952(88)90112-8. [DOI] [PubMed] [Google Scholar]
  15. Hopkins S. J., Humphreys M., Jayson M. I. Cytokines in synovial fluid. I. The presence of biologically active and immunoreactive IL-1. Clin Exp Immunol. 1988 Jun;72(3):422–427. [PMC free article] [PubMed] [Google Scholar]
  16. Hopkins S. J., Meager A. Cytokines in synovial fluid: II. The presence of tumour necrosis factor and interferon. Clin Exp Immunol. 1988 Jul;73(1):88–92. [PMC free article] [PubMed] [Google Scholar]
  17. Miossec P., Dinarello C. A., Ziff M. Interleukin-1 lymphocyte chemotactic activity in rheumatoid arthritis synovial fluid. Arthritis Rheum. 1986 Apr;29(4):461–470. doi: 10.1002/art.1780290402. [DOI] [PubMed] [Google Scholar]
  18. Mitchell D. M., Spitz P. W., Young D. Y., Bloch D. A., McShane D. J., Fries J. F. Survival, prognosis, and causes of death in rheumatoid arthritis. Arthritis Rheum. 1986 Jun;29(6):706–714. doi: 10.1002/art.1780290602. [DOI] [PubMed] [Google Scholar]
  19. Nagase H., Cawston T. E., De Silva M., Barrett A. J. Identification of plasma kallikrein as an activator of latent collagenase in rheumatoid synovial fluid. Biochim Biophys Acta. 1982 Mar 18;702(1):133–142. doi: 10.1016/0167-4838(82)90036-x. [DOI] [PubMed] [Google Scholar]
  20. Pettipher E. R., Higgs G. A., Henderson B. Interleukin 1 induces leukocyte infiltration and cartilage proteoglycan degradation in the synovial joint. Proc Natl Acad Sci U S A. 1986 Nov;83(22):8749–8753. doi: 10.1073/pnas.83.22.8749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Poole S., Bristow A. F., Selkirk S., Rafferty B. Development and application of radioimmunoassays for interleukin-1 alpha and interleukin-1 beta. J Immunol Methods. 1989 Jan 17;116(2):259–264. doi: 10.1016/0022-1759(89)90212-3. [DOI] [PubMed] [Google Scholar]
  22. Saklatvala J., Curry V. A., Sarsfield S. J. Purification to homogeneity of pig leucocyte catabolin, a protein that causes cartilage resorption in vitro. Biochem J. 1983 Nov 1;215(2):385–392. doi: 10.1042/bj2150385. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Saklatvala J., Dingle J. T. Identification of catabolin, a protein fro synovium which induces degradation of cartilage in organ culture. Biochem Biophys Res Commun. 1980 Oct 16;96(3):1225–1231. doi: 10.1016/0006-291x(80)90082-0. [DOI] [PubMed] [Google Scholar]
  24. Saklatvala J., Pilsworth L. M., Sarsfield S. J., Gavrilovic J., Heath J. K. Pig catabolin is a form of interleukin 1. Cartilage and bone resorb, fibroblasts make prostaglandin and collagenase, and thymocyte proliferation is augmented in response to one protein. Biochem J. 1984 Dec 1;224(2):461–466. doi: 10.1042/bj2240461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Saklatvala J., Sarsfield S. J., Townsend Y. Pig interleukin 1. Purification of two immunologically different leukocyte proteins that cause cartilage resorption, lymphocyte activation, and fever. J Exp Med. 1985 Oct 1;162(4):1208–1222. doi: 10.1084/jem.162.4.1208. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Saklatvala J. Tumour necrosis factor alpha stimulates resorption and inhibits synthesis of proteoglycan in cartilage. Nature. 1986 Aug 7;322(6079):547–549. doi: 10.1038/322547a0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Steinberg J. J., Hubbard J. R., Sledge C. B. Chondrocyte-mediated breakdown of cartilage. J Rheumatol. 1987 May;14(Spec No):55–58. [PubMed] [Google Scholar]
  28. Symons J. A., McDowell T. L., di Giovine F. S., Wood N. C., Capper S. J., Duff G. W. Interleukin 1 in rheumatoid arthritis: potentiation of immune responses within the joint. Lymphokine Res. 1989 Fall;8(3):365–372. [PubMed] [Google Scholar]
  29. Werb Z., Mainardi C. L., Vater C. A., Harris E. D., Jr Endogenous activiation of latent collagenase by rheumatoid synovial cells. Evidence for a role of plasminogen activator. N Engl J Med. 1977 May 5;296(18):1017–1023. doi: 10.1056/NEJM197705052961801. [DOI] [PubMed] [Google Scholar]
  30. Westacott C. I., Whicher J. T., Barnes I. C., Thompson D., Swan A. J., Dieppe P. A. Synovial fluid concentration of five different cytokines in rheumatic diseases. Ann Rheum Dis. 1990 Sep;49(9):676–681. doi: 10.1136/ard.49.9.676. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wood D. D., Ihrie E. J., Dinarello C. A., Cohen P. L. Isolation of an interleukin-1-like factor from human joint effusions. Arthritis Rheum. 1983 Aug;26(8):975–983. doi: 10.1002/art.1780260806. [DOI] [PubMed] [Google Scholar]
  32. Wood D. D., Ihrie E. J., Hamerman D. Release of interleukin-1 from human synovial tissue in vitro. Arthritis Rheum. 1985 Aug;28(8):853–862. doi: 10.1002/art.1780280804. [DOI] [PubMed] [Google Scholar]
  33. Yocum D. E., Esparza L., Dubry S., Benjamin J. B., Volz R., Scuderi P. Characteristics of tumor necrosis factor production in rheumatoid arthritis. Cell Immunol. 1989 Aug;122(1):131–145. doi: 10.1016/0008-8749(89)90154-8. [DOI] [PubMed] [Google Scholar]
  34. van de Loo A. A., van den Berg W. B. Effects of murine recombinant interleukin 1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation. Ann Rheum Dis. 1990 Apr;49(4):238–245. doi: 10.1136/ard.49.4.238. [DOI] [PMC free article] [PubMed] [Google Scholar]

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