Skip to main content
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1990 Apr;49(4):238–245. doi: 10.1136/ard.49.4.238

Effects of murine recombinant interleukin 1 on synovial joints in mice: measurement of patellar cartilage metabolism and joint inflammation.

A A van de Loo 1, W B van den Berg 1
PMCID: PMC1004046  PMID: 2339905

Abstract

Murine recombinant interleukin 1 was injected intra-articularly into mice. It induced a clear effect on patellar cartilage within 24 hours. A low dose of interleukin 1 (1 ng) elicited a significant reduction in [35S]sulphate incorporation (50%) into proteoglycans and an accelerated breakdown (twofold) of 35S prelabelled proteoglycan. Proteoglycan breakdown returned to normal rates (approximately 10%/day) 48 hours after a single interleukin 1 injection. Recovery of proteoglycan synthesis was delayed by up to 72 hours, however, which implies that repair of the depleted cartilage matrix is retarded. Interleukin 1 induced only minor joint inflammation, too slight to be held responsible for the strong suppression of proteoglycan synthesis. Vehement joint inflammation was found after repeated interleukin 1 injections. The plasma extravasation and massive infiltration and exudation of leucocytes, predominantly polymorphonuclear leucocytes, were not a mere summation of single interleukin 1 effects, but point to interleukin 1 induced local hypersensitivity. The cartilage matrices of patella and femur were heavily depleted. Measurement of the extent of loss of 35S prelabelled proteoglycan and the prolonged inhibition of [35S]sulphate incorporation indicate that both inhibition of proteoglycan synthesis and enhanced loss of proteoglycan contributed substantially to this depletion.

Full text

PDF
238

Images in this article

Selected References

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

  1. Arend W. P., Joslin F. G., Massoni R. J. Effects of immune complexes on production by human monocytes of interleukin 1 or an interleukin 1 inhibitor. J Immunol. 1985 Jun;134(6):3868–3875. [PubMed] [Google Scholar]
  2. Beck G., Habicht G. S., Benach J. L., Miller F. Interleukin 1: a common endogenous mediator of inflammation and the local Shwartzman reaction. J Immunol. 1986 Apr 15;136(8):3025–3031. [PubMed] [Google Scholar]
  3. 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]
  4. Benton H. P., Tyler J. A. Inhibition of cartilage proteoglycan synthesis by interleukin I. Biochem Biophys Res Commun. 1988 Jul 15;154(1):421–428. doi: 10.1016/0006-291x(88)90703-6. [DOI] [PubMed] [Google Scholar]
  5. Bevilacqua M. P., Pober J. S., Wheeler M. E., Cotran R. S., Gimbrone M. A., Jr Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines. J Clin Invest. 1985 Nov;76(5):2003–2011. doi: 10.1172/JCI112200. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bird T. A., Saklatvala J. Identification of a common class of high affinity receptors for both types of porcine interleukin-1 on connective tissue cells. Nature. 1986 Nov 20;324(6094):263–266. doi: 10.1038/324263a0. [DOI] [PubMed] [Google Scholar]
  7. Cavender D. E., Haskard D. O., Joseph B., Ziff M. Interleukin 1 increases the binding of human B and T lymphocytes to endothelial cell monolayers. J Immunol. 1986 Jan;136(1):203–207. [PubMed] [Google Scholar]
  8. Cavender D., Haskard D., Foster N., Ziff M. Superinduction of T lymphocyte-endothelial cell (EC) binding by treatment of EC with interleukin 1 and protein synthesis inhibitors. J Immunol. 1987 Apr 1;138(7):2149–2154. [PubMed] [Google Scholar]
  9. Cybulsky M. I., McComb D. J., Movat H. Z. Neutrophil leukocyte emigration induced by endotoxin. Mediator roles of interleukin 1 and tumor necrosis factor alpha 1. J Immunol. 1988 May 1;140(9):3144–3149. [PubMed] [Google Scholar]
  10. Danis V. A., March L. M., Nelson D. S., Brooks P. M. Interleukin-1 secretion by peripheral blood monocytes and synovial macrophages from patients with rheumatoid arthritis. J Rheumatol. 1987 Feb;14(1):33–39. [PubMed] [Google Scholar]
  11. Dinarello C. A. Interleukin-1 and the pathogenesis of the acute-phase response. N Engl J Med. 1984 Nov 29;311(22):1413–1418. doi: 10.1056/NEJM198411293112205. [DOI] [PubMed] [Google Scholar]
  12. Dinarello C. A. Interleukin-1. Rev Infect Dis. 1984 Jan-Feb;6(1):51–95. doi: 10.1093/clinids/6.1.51. [DOI] [PubMed] [Google Scholar]
  13. Dingle J. T., Page Thomas D. P., Hazleman B. The role of cytokines in arthritic diseases: in vitro and in vivo measurements of cartilage degradation. Int J Tissue React. 1987;9(4):349–354. [PubMed] [Google Scholar]
  14. 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]
  15. Gilman S. C. Activation of rabbit articular chondrocytes by recombinant human cytokines. J Rheumatol. 1987 Oct;14(5):1002–1007. [PubMed] [Google Scholar]
  16. Gladue R., Girard A., Newborg M. Enhanced antibacterial resistance in neutropenic mice treated with human recombinant interleukin-1 beta. Agents Actions. 1988 Jun;24(1-2):130–136. doi: 10.1007/BF01968091. [DOI] [PubMed] [Google Scholar]
  17. Granstein R. D., Margolis R., Mizel S. B., Sauder D. N. In vivo inflammatory activity of epidermal cell-derived thymocyte activating factor and recombinant interleukin 1 in the mouse. J Clin Invest. 1986 Mar;77(3):1020–1027. doi: 10.1172/JCI112354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hom J. T., Bendele A. M., Carlson D. G. In vivo administration with IL-1 accelerates the development of collagen-induced arthritis in mice. J Immunol. 1988 Aug 1;141(3):834–841. [PubMed] [Google Scholar]
  19. 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]
  20. Ikebe T., Hirata M., Koga T. Human recombinant interleukin 1-mediated suppression of glycosaminoglycan synthesis in cultured rat costal chondrocytes. Biochem Biophys Res Commun. 1986 Oct 15;140(1):386–391. doi: 10.1016/0006-291x(86)91102-2. [DOI] [PubMed] [Google Scholar]
  21. Krakauer T., Oppenheim J. J., Jasin H. E. Human interleukin 1 mediates cartilage matrix degradation. Cell Immunol. 1985 Mar;91(1):92–99. doi: 10.1016/0008-8749(85)90034-6. [DOI] [PubMed] [Google Scholar]
  22. Kruijsen M. W., van den Berg W. B., van de Putte L. B. Sequential alterations of periarticular structures in antigen-induced arthritis in mice. Histological observations on fibrous capsule, ligaments, bone and muscles, using whole joint sections. Br J Exp Pathol. 1983 Jun;64(3):298–305. [PMC free article] [PubMed] [Google Scholar]
  23. Le J., Vilcek J. Tumor necrosis factor and interleukin 1: cytokines with multiple overlapping biological activities. Lab Invest. 1987 Mar;56(3):234–248. [PubMed] [Google Scholar]
  24. Lens J. W., van den Berg W. B., van de Putte L. B. Quantitation of arthritis by 99mTc-uptake measurements in the mouse knee-joint: correlation with histological joint inflammation scores. Agents Actions. 1984 Jun;14(5-6):723–728. doi: 10.1007/BF01978915. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Moldawer L. L., Gelin J., Scherstén T., Lundholm K. G. Circulating interleukin 1 and tumor necrosis factor during inflammation. Am J Physiol. 1987 Dec;253(6 Pt 2):R922–R928. doi: 10.1152/ajpregu.1987.253.6.R922. [DOI] [PubMed] [Google Scholar]
  27. Movat H. Z., Burrowes C. E., Cybulsky M. I., Dinarello C. A. Acute inflammation and a Shwartzman-like reaction induced by interleukin-1 and tumor necrosis factor. Synergistic action of the cytokines in the induction of inflammation and microvascular injury. Am J Pathol. 1987 Dec;129(3):463–476. [PMC free article] [PubMed] [Google Scholar]
  28. Movat H. Z. Tumor necrosis factor and interleukin-1: role in acute inflammation and microvascular injury. J Lab Clin Med. 1987 Dec;110(6):668–681. [PubMed] [Google Scholar]
  29. Nouri A. M., Panayi G. S., Goodman S. M. Cytokines and the chronic inflammation of rheumatic disease. I. The presence of interleukin-1 in synovial fluids. Clin Exp Immunol. 1984 Feb;55(2):295–302. [PMC free article] [PubMed] [Google Scholar]
  30. Oppenheim J. J., Lew W., Akahoshi T., Matsushima K., Neta R. Aspects of cytokine induced modulation of immunity and inflammation with emphasis on interleukin 1. Arzneimittelforschung. 1988 Mar;38(3A):461–465. [PubMed] [Google Scholar]
  31. Ozaki Y., Ohashi T., Minami A., Nakamura S. Enhanced resistance of mice to bacterial infection induced by recombinant human interleukin-1a. Infect Immun. 1987 Jun;55(6):1436–1440. doi: 10.1128/iai.55.6.1436-1440.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Pasternak R. D., Hubbs S. J., Caccese R. G., Marks R. L., Conaty J. M., DiPasquale G. Interleukin-1 stimulates the secretion of proteoglycan- and collagen-degrading proteases by rabbit articular chondrocytes. Clin Immunol Immunopathol. 1986 Dec;41(3):351–367. doi: 10.1016/0090-1229(86)90006-1. [DOI] [PubMed] [Google Scholar]
  33. Pettipher E. R., Henderson B., Moncada S., Higgs G. A. Leucocyte infiltration and cartilage proteoglycan loss in immune arthritis in the rabbit. Br J Pharmacol. 1988 Sep;95(1):169–176. doi: 10.1111/j.1476-5381.1988.tb16561.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. 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]
  35. Pohlman T. H., Stanness K. A., Beatty P. G., Ochs H. D., Harlan J. M. An endothelial cell surface factor(s) induced in vitro by lipopolysaccharide, interleukin 1, and tumor necrosis factor-alpha increases neutrophil adherence by a CDw18-dependent mechanism. J Immunol. 1986 Jun 15;136(12):4548–4553. [PubMed] [Google Scholar]
  36. Rampart M., Williams T. J. Evidence that neutrophil accumulation induced by interleukin-1 requires both local protein biosynthesis and neutrophil CD18 antigen expression in vivo. Br J Pharmacol. 1988 Aug;94(4):1143–1148. doi: 10.1111/j.1476-5381.1988.tb11632.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ratcliffe A., Tyler J. A., Hardingham T. E. Articular cartilage cultured with interleukin 1. Increased release of link protein, hyaluronate-binding region and other proteoglycan fragments. Biochem J. 1986 Sep 1;238(2):571–580. doi: 10.1042/bj2380571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Saklatvala J., Bird T. A common class of receptors for the two types of porcine interleukin-1 on articular chondrocytes. Lymphokine Res. 1986;5 (Suppl 1):S99–104. [PubMed] [Google Scholar]
  39. Saklatvala J. Interleukin 1: purification and biochemical aspects of its action on cartilage. J Rheumatol. 1987 May;14(Spec No):52–54. [PubMed] [Google Scholar]
  40. Schnyder J., Payne T., Dinarello C. A. Human monocyte or recombinant interleukin 1's are specific for the secretion of a metalloproteinase from chondrocytes. J Immunol. 1987 Jan 15;138(2):496–503. [PubMed] [Google Scholar]
  41. Sedgwick A. D., Moore A. R., Al-Duaij A. Y., Edwards J. C., Willoughby D. A. Studies into the influence of carrageenan-induced inflammation on articular cartilage degradation using implantation into air pouches. Br J Exp Pathol. 1985 Aug;66(4):445–453. [PMC free article] [PubMed] [Google Scholar]
  42. Staruch M. J., Wood D. D. The adjuvanticity of interleukin 1 in vivo. J Immunol. 1983 May;130(5):2191–2194. [PubMed] [Google Scholar]
  43. Stimpson S. A., Dalldorf F. G., Otterness I. G., Schwab J. H. Exacerbation of arthritis by IL-1 in rat joints previously injured by peptidoglycan-polysaccharide. J Immunol. 1988 May 1;140(9):2964–2969. [PubMed] [Google Scholar]
  44. Tiku K., Tiku M. L., Liu S., Skosey J. L. Normal human neutrophils are a source of a specific interleukin 1 inhibitor. J Immunol. 1986 May 15;136(10):3686–3692. [PubMed] [Google Scholar]
  45. Tyler J. A. Articular cartilage cultured with catabolin (pig interleukin 1) synthesizes a decreased number of normal proteoglycan molecules. Biochem J. 1985 May 1;227(3):869–878. doi: 10.1042/bj2270869. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tyler J. A. Chondrocyte-mediated depletion of articular cartilage proteoglycans in vitro. Biochem J. 1985 Jan 15;225(2):493–507. doi: 10.1042/bj2250493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Wood D. D., Bayne E. K., Goldring M. B., Gowen M., Hamerman D., Humes J. L., Ihrie E. J., Lipsky P. E., Staruch M. J. The four biochemically distinct species of human interleukin 1 all exhibit similar biologic activities. J Immunol. 1985 Feb;134(2):895–903. [PubMed] [Google Scholar]
  48. 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]
  49. 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]
  50. Ziff M. Role of cytokines in rheumatoid synovitis. Recenti Prog Med. 1988 Jul-Aug;79(7-8):318–322. [PubMed] [Google Scholar]
  51. de Vries B. J., van den Berg W. B., Vitters E., van de Putte L. B. Quantitation of glycosaminoglycan metabolism in anatomically intact articular cartilage of the mouse patella: in vitro and in vivo studies with 35S-sulfate, 3H-glucosamine, and 3H-acetate. Rheumatol Int. 1986;6(6):273–281. doi: 10.1007/BF00541319. [DOI] [PubMed] [Google Scholar]
  52. van den Berg W. B., van de Loo F. A., Zwarts W. A., Otterness I. G. Effects of murine recombinant interleukin 1 on intact homologous articular cartilage: a quantitative and autoradiographic study. Ann Rheum Dis. 1988 Oct;47(10):855–863. doi: 10.1136/ard.47.10.855. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Publishing Group

RESOURCES