Skip to main content
SpringerLink
Log in

Colony-Stimulating Factors

A Potential Role in the Pathophysiology of Rheumatoid Arthritis

  • Leading Article
  • Published:
Clinical Immunotherapeutics Aims and scope Submit manuscript

Summary

Rheumatoid arthritis is characterised by infiltration of activated immunocompetent cells into synovial tissues. Activated macrophages, secreting proinflammatory cytokines, are found in rheumatoid arthritis synovitis in the presence of memory T cells, which are apparently not producing detectable quantities of those cytokines usually associated with monocyte activation.

Colony-stimulating factors (CSFs) can induce many of the features seen in rheumatoid arthritis synovitis, including monocyte activation, and may be involved in overproduction of macrophage-derived cytokines. The histological localisation of CSFs can help the understanding of their actions in the context of the pathology of the disease. Interactions between CSFs and their receptors on monocytes could at least implicate granulocyte-macrophage CSF in the pathophysiology of rheumatoid arthritis, thereby representing a potential target for novel forms of therapy in this chronic inflammatory disease.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Garrod A. The nature of gout and rheumatoid gout. London: Walton and Maberley, 1859

    Google Scholar 

  2. Firestein G, Xu W, Townsend K, et al. Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (IL-2 and IL-3) and presence of macrophage colony stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J Exp Med 1988; 168: 1573–86

    Article  PubMed  CAS  Google Scholar 

  3. Duke O, Panayi GS, Janossy G, et al. An immunohistochemical analysis of lymphocyte subpopulations and their microenvironment in the synovial membrane of patients with rheumatoid arthritis using monoclonal antibodies. Clin Exp Immunol 1982; 49: 22–30

    PubMed  CAS  Google Scholar 

  4. Burmester G, Jahn B, Rohwer P, et al. Differential expression of Ia antigens by rheumatoid synovial lining cells. J Clin Invest 1987; 80: 595–604

    Article  PubMed  CAS  Google Scholar 

  5. El-Gabalawy H, Gallatin M, Vazeux R, et al. Expression of ICAM-R (ICAM-3), a novel counter receptor for LFA-1 in rheumatoid synovium and non-rheumatoid synovium. Arthritis Rheum 1994; 37: 846–54

    Article  PubMed  CAS  Google Scholar 

  6. Hale L, Martin M, McCollum D, et al. Immunohistochemical analysis of the distribution of cell adhesion molecules within the inflammatory synovial microenvironment. Arthritis Rheum 1989; 32: 22–30

    Article  PubMed  CAS  Google Scholar 

  7. Kidd B, Moore K, Walters M, et al. Immunohistological features of synovitis in ankylosing spondylitis: a comparison with rheumatoid arthritis. Ann Rheum Dis 1989; 48: 92–8

    Article  PubMed  CAS  Google Scholar 

  8. Deleuran BW, Chu CQ, Field M, et al. Localization of interleukin-1α, type 1 interleukin-1 receptor and interleukin-1 receptor antagonist in the synovial membrane and cartilage/pannus junction in rheumatoid arthritis. Br J Rheumatol 1991; 31: 801–9

    Article  Google Scholar 

  9. Chu C, Field M, Feldmann M, et al. Localisation of tumour necrosis factor alpha in synovial tissue and at the cartilage/pannus junction in rheumatoid arthritis. Arthritis Rheum 1991; 34: 1125–32

    Article  PubMed  CAS  Google Scholar 

  10. Field M, Chu C, Feldmann M, et al. Interleukin-6 localisation in rheumatoid arthritis synovial membrane. Rheum Int 1991; 11: 45–50

    Article  CAS  Google Scholar 

  11. Firestein G, Zvaifler N. Peripheral blood and synovial fluid monocyte activation in inflammatory synovitis. II. Low levels of synovial fluid and synovial tissue interferon suggest that γ-interferon is not the primary macrophage activating factor. Arthritis Rheum 1987; 30: 864–71

    Article  PubMed  CAS  Google Scholar 

  12. Saxne T, Palladino M, Heingard D, et al. Detection of TNFγ but not TNFβ in rheumatoid arthritis synovial fluid and serum. Arthritis Rheum 1988; 31: 1041–5

    Article  PubMed  CAS  Google Scholar 

  13. Buchan G, Barrett K, Turner M, et al. Detection of activated T cell products in the rheumatoid joint using cDNA probes to interleukin-2, IL-2 receptor and interferon γ. Clin Exp Immunol 1988; 71: 295–301

    PubMed  CAS  Google Scholar 

  14. Moissec P, Naviliat M, D’Angeac D, et al. Low levels of IL-4 and high levels of TGFβ in rheumatoid synovitis. Arthritis Rheum 1990; 33: 1180–7

    Article  Google Scholar 

  15. Brennan FM, Field M, Chu CQ, et al. Cytokine expression in rheumatoid arthritis. Br J Rheumatol 1991; 30 Suppl. 2: 76–80

    PubMed  Google Scholar 

  16. Farrar M, Schreiber R. The molecular biology of interferon γ and its receptor. Annu Rev Immunol 1994; 11: 571–612

    Article  Google Scholar 

  17. Fischer HG, Frosch S, Reske K, et al. Granulocyte macrophage colony stimulating factor activates macrophages derived from bone marrow cultures to synthesis of MHC Class II molecules and to augment antigen presentation function. J Immunol 1988; 141: 3882–8

    PubMed  CAS  Google Scholar 

  18. Williamson DJ, Begley CG, Vadas MA, et al. The detection and initial characterisation of colony stimulating factors in synovial fluid. Clin Exp Immunol 1988; 72: 67–73

    PubMed  CAS  Google Scholar 

  19. Alvaro-Garcia JM, Zwaifler NJ, Brown CB, et al. Cytokines in chronic inflammatory arthritis. VI. Analysis of the synovial cells in granulocyte macrophage colony stimulating factor production and gene expression in rheumatoid arthritis and its regulation by IL-1 and TNFα. J Immunol 1991; 146: 3365–71

    Google Scholar 

  20. Alvaro-Gracia JM, Zwaifler NJ, Firestein G. Cytokines in chronic inflammatory arthritis. IV. Granulocyte macrophage colony stimulating factor mediated induction of class II antigen on human monocytes: a possible role in rheumatoid arthritis. J Exp Med 1989; 170: 865–75

    Article  PubMed  CAS  Google Scholar 

  21. Gamble JR, Elliot MJ, Jaipargas E, et al. Regulation of human monocyte adherence by granulocyte macrophage colony stimulating factor. Proc Natl Acad Sci USA 1989; 86: 7169–73

    Article  PubMed  CAS  Google Scholar 

  22. De Vreis E, Willemse P, Beisma B, et al. Flare up of rheumatoid arthritis during granulocyte macrophage colony stimulating factor treatment after chemotherapy. Lancet 1991; 338: 517–8

    Article  Google Scholar 

  23. Hazenberg B, Van Leeuwen M, Van Rijswijk M, et al. Correction of granulocytopaenia of Felty’s syndrome by granulocyte macrophage colony stimulating factor: simultaneous induction of interleukin 6 release and flare up of the arthritis. Blood 1989; 74: 2769–70

    PubMed  CAS  Google Scholar 

  24. Williamson DJ, Begley CG, Vadas MA, et al. The detection and initial characterisation of colony stimulating factors in synovial fluid. Clin Exp Immunol 1988; 72: 67–73

    PubMed  CAS  Google Scholar 

  25. Schibler K, Leichty K, White W, et al. Production of granulocyte colony stimulating factor in vitro by monocytes from preterm and term neonates. Blood 1993; 82: 2478–84

    PubMed  CAS  Google Scholar 

  26. Spiekermann K, Emmendoerffer A, Eisner J, et al. Altered surface marker expression and function of G-CSF induced neutrophils from test subjects and patients under chemotherapy. Br J Haematol 1994; 87: 31–8

    Article  PubMed  CAS  Google Scholar 

  27. Yuo A, Kitagawa S, Ohsaka A, et al. Recombinant human granulocyte colony stimulating factor as an activator of human granulocytes: potentiation of responses triggered by receptor mediated agonists and stimulation of C3bi receptor expression and adherence. Blood 1989; 74: 2144–9

    PubMed  CAS  Google Scholar 

  28. Repp R, Valerius T, Sendler A, et al. Neutrophils express the high affinity receptor for IgG (Fc γR1, CD64) after in vivo application of granulocyte colony stimulating factor. Blood 1991; 78: 885–9

    PubMed  CAS  Google Scholar 

  29. Weisbart RH, Golde DW, Clark SC, et al. Human granulocyte macrophage colony stimulating factor is a neutrophil activator. Nature 1985; 314: 361–3

    Article  PubMed  CAS  Google Scholar 

  30. Lindemann A, Herrmann F, Oster W, et al. Haematologic effects of recombinant human granulocyte colony stimulating factor in patients with malignancy. Blood 1989; 74: 2644–51

    PubMed  CAS  Google Scholar 

  31. Leische G, Burgess A. Granulocyte colony stimulating factor and granulocyte macrophage colony stimulating factor. N Engl J Med 1992; 327: 99–106

    Article  Google Scholar 

  32. Lopez A, Williamson J, Gamble J, et al. Recombinant granulocyte macrophage colony stimulating factor stimulates in vitro mature neutrophil and eosinophil functions, surface receptors and survival. J Clin Invest 1986; 78: 1220–8

    Article  PubMed  CAS  Google Scholar 

  33. Pouliot M, McDonald P, Borgeat P, et al. Granulocyte macrophage colony stimulating factor stimulates the expression of the 5-lipoxygenase-activating protein (FLAP) in human neutrophils. J Exp Med 1994; 179: 1225–32

    Article  PubMed  CAS  Google Scholar 

  34. Lindemann A, Reidel D, Oster W, et al. Granulocyte macrophage colony stimulating factor induces cytokine secretion by human polymorphonuclear neutrophils. J Clin Invest 1988; 83: 1308–12

    Article  Google Scholar 

  35. Khwaja A, Johnson B, Addison I, et al. In vivo effects of macrophage colony stimulating factor on human monocyte function. Br J Haematol 1991; 77: 25–31

    Article  PubMed  CAS  Google Scholar 

  36. Sampson-Johannes A, Carlino J. Enhancement of human monocyte tumoricidal activity by recombinant M-CSF. J Immunol 1988; 141: 3680–6

    PubMed  CAS  Google Scholar 

  37. Warren M, Ralph P. Macrophage growth factor CSF-1 stimulates human monocyte production of interferon, tumour necrosis factor and colony stimulating factor. J Immunol 1986; 137: 2281–5

    PubMed  CAS  Google Scholar 

  38. Motoyoshi K, Yoshida K, Hatake K, et al. Recombinant and native urinary colony stimulating factor directly augments granulocyte and granulocyte macrophage colony stimulating factor production by human peripheral blood monocytes. Exp Haematol 1989; 17: 68–71

    CAS  Google Scholar 

  39. Feldmann M, Brennan FM, Field M, et al. Pathogenesis of rheumatoid arthritis: cellular and cytokine interactions. In: Smolen JS, Kalden JR, Maini RN, editors. Rheumatoid arthritis. Berlin: Springer Verlag, 1992: 41–54

    Chapter  Google Scholar 

  40. Brennan F, Chantrey D, Jackson A, et al. Inhibitory effects of TNFα antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 1989; 2: 244–7

    Article  PubMed  CAS  Google Scholar 

  41. Keffer J, Probert L, Cazlaris H, et al. Transgenic mice expressing human tumour necrosis factor: a predictive genetic model of arthritis. EMBO J 1991; 10: 4025–31

    PubMed  CAS  Google Scholar 

  42. Elliot MJ, Maini RN, Feldmann M, et al. Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor α (cA2) versus placebo in rheumatoid arthritis. Lancet 1994; 344: 1105–10

    Article  Google Scholar 

  43. Cannistra SA, Rambaldi A, Spriggs DR, et al. Human granulocyte macrophage colony stimulating factor induces expression of the tumour necrosis factor gene by U937 cell line and normal human monocytes. J Clin Invest 1987; 79: 1720–8

    Article  PubMed  CAS  Google Scholar 

  44. Danis V, Franic G, Rathjen D, et al. Effects of granulocyte macrophage colony stimulating factor (GM-CSF), IL-2, interferon-γ (INF-γ), tumour necrosis factor (TNFα) and IL-6 on the production of immunoreactive IL-1 and TNFα by human monocytes. Clin Exp Immunol 1991; 85: 143–50

    Article  PubMed  CAS  Google Scholar 

  45. Malyak M, Swaney R, Arend W. Levels of synovial fluid interleukin-1 receptor antagonist in rheumatoid arthritis and other arthropathies. Arthritis Rheum 1993; 36: 781–9

    Article  PubMed  CAS  Google Scholar 

  46. Gearing A, Metcalf D, Moore J, et al. Elevated levels of GM-CSF and IL-1 in the serum and pleural cavities of GM-CSF transgenic mice. Immunology 1989; 67: 216–20

    PubMed  CAS  Google Scholar 

  47. Chantrey D, Turner M, Brennan F, et al. Granulocyte macrophage colony stimulating factor induces both HLA DR expression and cytokine production by human monocytes. Cytokine 1990; 2: 60–7

    Article  Google Scholar 

  48. Hart P, Whitty G, Picolli D, et al. Synergistic activation of human monocytes by granulocyte macrophage colony stimulating factor and interferon γ. Increased production of TNFα but not IL-1 activity. J Immunol 1991; 141: 1516–21

    Google Scholar 

  49. Hamilton J, Whitty G, Stanton H, et al. Effects of macrophage colony stimulating factor on human monocytes: induction of expression of urokinase type plasminogen activator, but not secreted prostaglandin E2, IL-6, IL-1 or TNFα. J Leukoc Biol 1993; 53: 707–14

    PubMed  CAS  Google Scholar 

  50. Haworth C, Brennan F, Chantrey D, et al. Expression of granulocyte macrophage colony stimulating factor in rheumatoid arthritis: regulation by tumour necrosis factor [abstract]. Eur J Immunol 1991; 21: 2575–9

    Article  PubMed  CAS  Google Scholar 

  51. Chu CC, Field M, Allard SA, et al. Detection of cytokines at the cartilage/pannus junction in patients with rheumatoid arthritis: implications for the role of cytokines in cartilage destruction and repair. Br J Rheumatol 1992; 31: 653–61

    Article  PubMed  CAS  Google Scholar 

  52. Field M, Clinton L. Granulocyte macrophage colony stimulating factor in rheumatoid arthritis. Clin Rheumatol 1994; 13: 178

    Google Scholar 

  53. Kaushansky K. Control of granulocyte macrophage colony stimulating factor in normal endothelial cells by positive and negative regulatory elements. J Immunol 1989; 143: 2525–9

    PubMed  CAS  Google Scholar 

  54. Zsebo K, Yushenkoff V, Schiffer S, et al. Vascular endotheial cells and granulopoiesis: interleukin-1 stimulates release of G-CSF and GM-CSF. Blood 1988; 71: 99–103

    PubMed  CAS  Google Scholar 

  55. Field M, Clinton L. Expression of GM-CSF receptor in rheumatoid arthritis. Lancet 1993; 342: 1244

    Article  PubMed  CAS  Google Scholar 

  56. Gliniak B, Rohrschneider L. Expression of the M-CSF receptor is controlled post-transcriptionally by the dominant actions of GM-CSF or multi-CSF. Cell 1990; 63: 1073–83

    Article  PubMed  CAS  Google Scholar 

  57. Day R. Slow acting anti-rheumatic drugs I. In: Klippel JH, Dieppe PA, editors. Rheumatology. London: Mosby Year Book Europe, 1994: 8.12.1–10

    Google Scholar 

  58. Furst D, Clements P. Slow acting anti-rheumtic drugs II. In: Klippel JH, Dieppe PA, editors. Rheumatology. London: Mosby Year Book Europe, 1994: 8.13.1–8

    Google Scholar 

  59. Hamilton J, Williams N. In vitro inhibition of myelopoiesis by gold salts and D-penicillamine. J Rheumatol 1985; 12: 892–6

    PubMed  CAS  Google Scholar 

  60. Yanni G, Farahat M, Poston R, et al. Cytokine expression in rheumatoid arthritis synovial membrane following treatment with intramuscular gold. Arthritis Rheum 1992; 35 Suppl. 9: S108

    Google Scholar 

  61. Matsubara T, Ziff M. Inhibition of human endothelial cell proliferation by gold compounds. J Clin Invest 1987; 79: 1440–46

    Article  PubMed  CAS  Google Scholar 

  62. Madhok R, Wijelath E, Smith J, et al. Is the beneficial effect of sulphasalazine due to inhibition of synovial neovascularisation? J Rheumatol 1991; 18: 199–202

    PubMed  CAS  Google Scholar 

  63. Hamilton J. Rheumatoid arthritis: opposing actions of haemopoietic growth factors and slow acting anti-rheumatic drugs. Lancet 1993; 342: 536–9

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Centre for Rheumatic Diseases, Glasgow Royal Infirmary, Alexandra Parade, Glasgow, G31 2ER, Scotland

    Max Field

Authors
  1. Max Field
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Field, M. Colony-Stimulating Factors. Clin. Immunother. 3, 255–261 (1995). https://doi.org/10.1007/BF03259277

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03259277

Keywords

Search

Navigation