Skip to main content
NCBI home page
Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1995 Aug;54(8):654–661. doi: 10.1136/ard.54.8.654

Detection of cytokine producing cells in the synovial membrane from patients with rheumatoid arthritis.

A K Ulfgren 1, S Lindblad 1, L Klareskog 1, J Andersson 1, U Andersson 1
PMCID: PMC1009963  PMID: 7677442

Abstract

OBJECTIVES--To develop and evaluate a new immunohistochemical method to study the localisation and phenotype of individual cytokine producing cells in synovial biopsy specimens in rheumatoid arthritis. METHODS--Cryopreserved sections of synovial tissue from nine patients with rheumatoid arthritis were incubated with carefully selected cytokine specific antibodies detecting 19 different cytokines, after fixation of the specimens with paraformaldehyde and using saponin to permeabilise the cell membranes. RESULTS--The immunohistochemical method yielded reproducible and distinct staining patterns, in which the cytokines accumulated mainly in the Golgi apparatus of producer cells, indicating that the method preferentially detected local synthesis rather than cytokine uptake. The cytokine production patterns varied considerably between biopsy specimens from different patients. CONCLUSION--The present modified immunohistochemical method may provide a simple and rapid way to determine the local production of a wide array of cytokines in the synovium. The data obtained with this method also indicated that more T cell derived cytokines than previously recognised were present in active synovitis, as located and sampled by arthroscopy.

Full text

PDF
654

Images in this article

657Image
on p.657
658Image
on p.658

Selected References

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

  1. Abrams J. S., Roncarolo M. G., Yssel H., Andersson U., Gleich G. J., Silver J. E. Strategies of anti-cytokine monoclonal antibody development: immunoassay of IL-10 and IL-5 in clinical samples. Immunol Rev. 1992 Jun;127:5–24. doi: 10.1111/j.1600-065x.1992.tb01406.x. [DOI] [PubMed] [Google Scholar]
  2. Agace W., Hedges S., Andersson U., Andersson J., Ceska M., Svanborg C. Selective cytokine production by epithelial cells following exposure to Escherichia coli. Infect Immun. 1993 Feb;61(2):602–609. doi: 10.1128/iai.61.2.602-609.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andersson G., Ekre H. P., Alm G., Perlmann P. Monoclonal antibody two-site ELISA for human IFN-gamma. Adaptation for determinations in human serum or plasma. J Immunol Methods. 1989 Dec 20;125(1-2):89–96. doi: 10.1016/0022-1759(89)90081-1. [DOI] [PubMed] [Google Scholar]
  4. Andersson J., Abrams J., Björk L., Funa K., Litton M., Agren K., Andersson U. Concomitant in vivo production of 19 different cytokines in human tonsils. Immunology. 1994 Sep;83(1):16–24. [PMC free article] [PubMed] [Google Scholar]
  5. Andersson U., Adolf G., Dohlsten M., Möller G., Sjögren H. O. Characterization of individual tumor necrosis factor alpha-and beta-producing cells after polyclonal T cell activation. J Immunol Methods. 1989 Oct 24;123(2):233–240. doi: 10.1016/0022-1759(89)90227-5. [DOI] [PubMed] [Google Scholar]
  6. Arnett F. C., Edworthy S. M., Bloch D. A., McShane D. J., Fries J. F., Cooper N. S., Healey L. A., Kaplan S. R., Liang M. H., Luthra H. S. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. doi: 10.1002/art.1780310302. [DOI] [PubMed] [Google Scholar]
  7. Brennan F. M., Zachariae C. O., Chantry D., Larsen C. G., Turner M., Maini R. N., Matsushima K., Feldmann M. Detection of interleukin 8 biological activity in synovial fluids from patients with rheumatoid arthritis and production of interleukin 8 mRNA by isolated synovial cells. Eur J Immunol. 1990 Sep;20(9):2141–2144. doi: 10.1002/eji.1830200938. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Burmester G. R., Yu D. T., Irani A. M., Kunkel H. G., Winchester R. J. Ia+ T cells in synovial fluid and tissues of patients with rheumatoid arthritis. Arthritis Rheum. 1981 Nov;24(11):1370–1376. doi: 10.1002/art.1780241106. [DOI] [PubMed] [Google Scholar]
  10. Chu C. Q., Field M., Feldmann M., Maini R. N. Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis. Arthritis Rheum. 1991 Sep;34(9):1125–1132. doi: 10.1002/art.1780340908. [DOI] [PubMed] [Google Scholar]
  11. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  12. Dolhain R. J., Andersson U., ter Haar N. T., Brinkman B. M., Verweij C. L., Daha M. R., Breedveld F. C., Miltenburg A. M. Detection of intracellular interferon-gamma by light microscopy using an immunoperoxidase technique: correlation with the corresponding mRNA and protein product. J Leukoc Biol. 1993 Dec;54(6):545–551. doi: 10.1002/jlb.54.6.545. [DOI] [PubMed] [Google Scholar]
  13. Firestein G. S., Berger A. E., Tracey D. E., Chosay J. G., Chapman D. L., Paine M. M., Yu C., Zvaifler N. J. IL-1 receptor antagonist protein production and gene expression in rheumatoid arthritis and osteoarthritis synovium. J Immunol. 1992 Aug 1;149(3):1054–1062. [PubMed] [Google Scholar]
  14. Firestein G. S., Xu W. D., Townsend K., Broide D., Alvaro-Gracia J., Glasebrook A., Zvaifler N. J. Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J Exp Med. 1988 Nov 1;168(5):1573–1586. doi: 10.1084/jem.168.5.1573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Firestein G. S., Zvaifler N. J. How important are T cells in chronic rheumatoid synovitis? Arthritis Rheum. 1990 Jun;33(6):768–773. doi: 10.1002/art.1780330602. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Hirano T., Matsuda T., Turner M., Miyasaka N., Buchan G., Tang B., Sato K., Shimizu M., Maini R., Feldmann M. Excessive production of interleukin 6/B cell stimulatory factor-2 in rheumatoid arthritis. Eur J Immunol. 1988 Nov;18(11):1797–1801. doi: 10.1002/eji.1830181122. [DOI] [PubMed] [Google Scholar]
  18. Husby G., Williams R. C., Jr Immunohistochemical studies of interleukin-2 and gamma-interferon in rheumatoid arthritis. Arthritis Rheum. 1985 Feb;28(2):174–181. doi: 10.1002/art.1780280212. [DOI] [PubMed] [Google Scholar]
  19. Klareskog L., Forsum U., Malmnäs Tjernlund U. K., Kabelitz D., Wigren A. Appearance of anti-HLA-DR-reactive cells in normal and rheumatoid synovial tissue. Scand J Immunol. 1981 Aug;14(2):183–192. doi: 10.1111/j.1365-3083.1981.tb00198.x. [DOI] [PubMed] [Google Scholar]
  20. Klareskog L., Rubin K., Holmdahl R. Binding of collagen type II to rheumatoid synovial cells. Scand J Immunol. 1986 Dec;24(6):705–714. doi: 10.1111/j.1365-3083.1986.tb02190.x. [DOI] [PubMed] [Google Scholar]
  21. Lindblad S., Hedfors E. Intraarticular variation in synovitis. Local macroscopic and microscopic signs of inflammatory activity are significantly correlated. Arthritis Rheum. 1985 Sep;28(9):977–986. doi: 10.1002/art.1780280904. [DOI] [PubMed] [Google Scholar]
  22. Lindblad S., Klareskog L., Hedfors E., Forsum U., Sundström C. Phenotypic characterization of synovial tissue cells in situ in different types of synovitis. Arthritis Rheum. 1983 Nov;26(11):1321–1332. doi: 10.1002/art.1780261104. [DOI] [PubMed] [Google Scholar]
  23. McKenzie A. N., Culpepper J. A., de Waal Malefyt R., Brière F., Punnonen J., Aversa G., Sato A., Dang W., Cocks B. G., Menon S. Interleukin 13, a T-cell-derived cytokine that regulates human monocyte and B-cell function. Proc Natl Acad Sci U S A. 1993 Apr 15;90(8):3735–3739. doi: 10.1073/pnas.90.8.3735. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Miossec P., Naviliat M., Dupuy d'Angeac A., Sany J., Banchereau J. Low levels of interleukin-4 and high levels of transforming growth factor beta in rheumatoid synovitis. Arthritis Rheum. 1990 Aug;33(8):1180–1187. doi: 10.1002/art.1780330819. [DOI] [PubMed] [Google Scholar]
  25. Olofsson A., Miyazono K., Kanzaki T., Colosetti P., Engström U., Heldin C. H. Transforming growth factor-beta 1, -beta 2, and -beta 3 secreted by a human glioblastoma cell line. Identification of small and different forms of large latent complexes. J Biol Chem. 1992 Sep 25;267(27):19482–19488. [PubMed] [Google Scholar]
  26. Panayi G. S., Lanchbury J. S., Kingsley G. H. The importance of the T cell in initiating and maintaining the chronic synovitis of rheumatoid arthritis. Arthritis Rheum. 1992 Jul;35(7):729–735. doi: 10.1002/art.1780350702. [DOI] [PubMed] [Google Scholar]
  27. Raqib R., Lindberg A. A., Wretlind B., Bardhan P. K., Andersson U., Andersson J. Persistence of local cytokine production in shigellosis in acute and convalescent stages. Infect Immun. 1995 Jan;63(1):289–296. doi: 10.1128/iai.63.1.289-296.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sander B., Andersson J., Andersson U. Assessment of cytokines by immunofluorescence and the paraformaldehyde-saponin procedure. Immunol Rev. 1991 Feb;119:65–93. doi: 10.1111/j.1600-065x.1991.tb00578.x. [DOI] [PubMed] [Google Scholar]
  29. Taketazu F., Kato M., Gobl A., Ichijo H., ten Dijke P., Itoh J., Kyogoku M., Rönnelid J., Miyazono K., Heldin C. H. Enhanced expression of transforming growth factor-beta s and transforming growth factor-beta type II receptor in the synovial tissues of patients with rheumatoid arthritis. Lab Invest. 1994 May;70(5):620–630. [PubMed] [Google Scholar]
  30. Xu W. D., Firestein G. S., Taetle R., Kaushansky K., Zvaifler N. J. Cytokines in chronic inflammatory arthritis. II. Granulocyte-macrophage colony-stimulating factor in rheumatoid synovial effusions. J Clin Invest. 1989 Mar;83(3):876–882. doi: 10.1172/JCI113971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Yanni G., Nabil M., Farahat M. R., Poston R. N., Panayi G. S. Intramuscular gold decreases cytokine expression and macrophage numbers in the rheumatoid synovial membrane. Ann Rheum Dis. 1994 May;53(5):315–322. doi: 10.1136/ard.53.5.315. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES