Immunopathogenetic mechanisms of arthritis and modes of action of antirheumatic therapies

  • A. C. Allison


The aetiology of rheumatoid arthritis (RA) remains unknown. There is no evidence for bacterial involvement, which is the case in rheumatic fever, Lyme arthritis and Reiter’s disease. Although acute viral infections such as rubella can produce arthritis, there is no evidence that rubella or any other virus is specifically associated with RA. While responses of lymphocytes from RA patients to Epstein-Barr virus have provided interesting information1, no causal relationship has been established. The pattern of disease, and responses to immunosuppressive drugs, leave little doubt that immune reactions to an exogenous agent or agents, or to host components, are involved. In other words, the pathogenesis of RA is an immunologically driven, chronic inflammatory reaction. There are certainly autoimmune manifestations in RA, notably production of antiglobulins or rheumatoid factors; but the aetiology of autoimmunity is itself obscure and likely to be due to complex interactions of host genetic and environmental factors2,3. Whether rheumatoid factors play a causal role in RA is an unresolved question, which will be discussed below.


Rheumatoid Arthritis Major Histocompatibility Complex Synovial Fluid Rheumatoid Factor Rheumatoid Arthritis Synovia 
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  1. 1.
    Hasler, F., Bluestein, H.G., Zwaifler, N.J. and Epstein, L.B. (1983). Analysis of the defects responsible for the impaired regulation of EBV-induced B-cell proliferation by rheumatoid arthritis lymphocytes. II. Role of monocytes and the increased sensitivity of rheumatoid arthritis lymphocytes to prostaglandin E. J. Immunol, 131, 768–72Google Scholar
  2. 2.
    Allison, A.C. (1977). Autoimmune diseases: Concepts of pathogenesis and control. In Talal, N. (ed.) Autoimmunity: Genetic, Virologie, and Clinical Aspects. pp. 92–139. (New York, London: Academic Press)Google Scholar
  3. 3.
    Schwartz, R.S. and Rose, N.R. (eds.) (1986). Autoimmunity: experimental and clinical aspects. Ann. NY. Acad. Sci., 475, 1–427Google Scholar
  4. 4.
    Budd, R.C., Cerottini, J.-C., Horvath, C., Bron, C., Pedrazzini, T., Howe, R.C. and MacDonald, H.R. (1987). Distinction of virgin and memory T lymphocytes. J. Immunol., 138, 3120–9PubMedGoogle Scholar
  5. 5.
    Klickstein, L.B., Shapleigh, C. and Goetzl, E.J. (1980). Lipoxygenation of arachidonic acid as a source of polymorphonuclear chemotactic factors in synovial fluid and tissue in rheumatoid arthritis and spondyloarthritis. J. Clin. Invest., 66, 1166–70PubMedCrossRefGoogle Scholar
  6. 6.
    Zwaifler, N.J. (1973). The immunopathology of joint inflammation in rheumatoid arthritis. Adv. Immunol., 16, 265–336CrossRefGoogle Scholar
  7. 7.
    Mohr, W., Menninger, H. and Putzier, R. (1979). Morphologische Hinweise für die Beteiligung an der rheumatischen Knorpel-destruktion. Bull Schweiz. Akad. Med. Wiss., 35, 443–51PubMedGoogle Scholar
  8. 8.
    Fassbender, H.G. and Simmling-Annefeld, M. (1983). The potential aggressiveness of synovial tissue in rheumatoid arthritis. J. Pathol, 139, 399–406PubMedCrossRefGoogle Scholar
  9. 9.
    Souza, L.M., Boone, T.C., Gabrilone, J., Lai, P.H., Zsebo, K.M., Murdock, D.C., Chazin, V.R., Bruszewski, J., Lu, H., Chen, K.K., Barendt, J., Platzer, E., Moore, M.A.S., Mertelsmann, R. and Welta, K. (1986). Recombinant human granulocyte colony-stimulating factor: effects on normal and leukemic myeloid cells. Science, 232, 61–5PubMedCrossRefGoogle Scholar
  10. 10.
    Kawasaki, E.S., Ladner, M.B., Wang, A.M., Van Arsdell, J., Warren, M.K., Coyne, M.Y., Schweickart, V.L., Lee, M.-T., Wilson, K.J., Boosman, A., Stanley, E.R., Ralph, P. and Mark, D.F. (1985). Molecular cloning of a complementary DNA encoding human macrophage-specific colony-stimulating factor (CSF-1). Science, 230, 291–4PubMedCrossRefGoogle Scholar
  11. 11.
    Cantrell, M.A., Anderson, D., Cerretti, D.P., Price, V., McKereghan, K., Tushinski, R.J., Mochizuki, D.Y., Larsen, A., Grabstein, K., Gillis, S. and Cosman, D. (1985). Cloning, sequence and expression of a human granulocyte/macrophage colony-stimulating factor. Proc. Natl Acad. Sci. USA, 82, 6250–4PubMedCrossRefGoogle Scholar
  12. 12.
    Sherr, C.J., Rettenmeier, C.W., Socca, R., Roussel, M.F., Look, A.T. and Stanley, E.R. (1985). The c-fms proto-oncogene product is related to the receptor for mononuclear phagocyte growth factor, CSF-1. Cell, 41, 665–76PubMedCrossRefGoogle Scholar
  13. 13.
    Nishizuka, Y. (1986). Perspectives on the role of protein kinase C in stimulus-response coupling. J. Natl. Cancer Inst., 763, 363–70Google Scholar
  14. 14.
    Berridge, M.J. and Irvine, R.F. (1984). Inositol triphosphate, a novel second messenger in cellular signal transduction. Nature, 312, 315–21PubMedCrossRefGoogle Scholar
  15. 15.
    Waters, R. and Allison, A.C. (1987). Differentiation of promonocytic and promyelocytic human cell lines induced by 5-lipoxygenase inhibitors and leukotriene D4 antagonists. (Submitted)Google Scholar
  16. 16.
    Burmester, G.R., Dimitriu-Bona, A., Waters, S.J. and Winchester, R.J. (1983). Identification of three major synovial lining cell populations by monoclonal antibodies directed to la antigens and antigens associated with monocytes/macrophages and fibroblasts. Scand. J. Immunol., 17, 69–82PubMedCrossRefGoogle Scholar
  17. 17.
    Duke, O., Panayi, G.S., Janossy, G. and Poulter, L.W. (1982). Immuno-histological analysis of the lymphocytic infiltrates of rheumatoid synovial membrane using monoclonal antibodies. Ann. Rheum. Dis., 41, 192–3CrossRefGoogle Scholar
  18. 18.
    Hoefsmit, E.C.M., Balfour, B.M., Kamperdijk, E.W.A. et al. (1979). Cells containing Birbeck granules in the lymph and the lymph nodes. In Muller-Bucholz, W. and Moller-Hermelinck, H.K. (eds.) Function and Structure of the Immune System. Adv. Exp. Med. Biol, 114, 389–98Google Scholar
  19. 19.
    Peeler, J.S. and Niederkorn, J.Y. (1986). Antigen presentation by Langerhans cells in vivo: donor-derived Ia+ Langerhans cells are required for induction of delayed hypersensitivity but not for cytotoxic T lymphocyte responses to alloantigens. J. Immunol., 136, 4362–71PubMedGoogle Scholar
  20. 20.
    Meijer, C.J.L.M., de Graaf-Reitsma, C.B. Lafeber, G.J.M. and Cats, A. (1982). In situ localization of lymphocyte subsets in synovial membranes of patients with rheumatoid arthritis with monoclonal antibodies. J. Rheumatol, 9, 359–65PubMedGoogle Scholar
  21. 21.
    Klaus, G.G., Humphrey, J.H., Kunkl, A. and Dongworth, D.W. (1980). The follicular dendritic cell: its role in antigen presentation in the generation of immunological memory. Immunol Rev., 53, 3–28PubMedCrossRefGoogle Scholar
  22. 22.
    Tew, J.G., Phipps, R.P. and Mandel, T.E. (1980). The maintenance and regulation of the humoral immune response: persisting antigen and the role of follicular antigen-binding dendritic cells as accessory cells. Immunol Rev., 53, 175–201PubMedCrossRefGoogle Scholar
  23. 23.
    Mannick, M. and Nardella, F.A. (1983). Self-associating IgG-rheumatoid factors. In Shiokawa, Y., Abe, T. and Yamauchi, Y. (eds.) New Horizons in Rheumatoid Arthritis, pp. 124–31. (Amsterdam: Excerpta Medica)Google Scholar
  24. 24.
    Fassbender, H. (1980). Pathology of Rheumatoid Disease, pp. 2–143. (Heidelberg: Springer)Google Scholar
  25. 25.
    Young, C.L., Adamson, T.C. III, Vaughan, J.H. and Fox, R.I. (1984). Immunohistologic characterization of synovial membrane lymphocytes in rheumatoid arthritis. Arthr. Rheum., 27, 32–9CrossRefGoogle Scholar
  26. 26.
    Smiley, J.D., Sachs, C. and Ziff, M. (1968). In vitro synthesis of immunoglobulin by rheumatoid synovial membrane. J. Clin. Invest., 47, 624–32PubMedCrossRefGoogle Scholar
  27. 27.
    Wernick, R.M., Lipsky, P.E., Marban-Arcos, E., Maliakkol, J.J., Edelbaum, D. and Ziff, M. (1985). IgG and IgM rheumatoid factor synthesis in rheumatoid synovial membrane cell cultures. Arthr. Rheum., 28, 742–51CrossRefGoogle Scholar
  28. 28.
    Sliwinski, A J. and Zvaifler, N.J. (1970). In vivo synthesis of IgG by the rheumatoid synovial membrane. J. Lab. Clin. Med., 76, 304–10PubMedGoogle Scholar
  29. 29.
    Al-Balaghi, S., Strom, H. and Möller, E. (1984). B-cell differentiation factor in synovial fluid of patients with rheumatoid arthritis. Immunol Rev., 78, 7–23PubMedCrossRefGoogle Scholar
  30. 30.
    Bell, D.A. and Pinto, J. (1984). Distribution of activated B lymphocytes in the circulation and synovial fluid in rheumatoid arthritis. Clin. Immunol. Immunopathol, 31, 272–81PubMedCrossRefGoogle Scholar
  31. 31.
    Teodorescu, M., Chang, J.L. and Skosey, J.L. (1981). Polyclonal B-cell activator associated with alpha-2-macroglobulin in the serum of patients with rheumatoid arthritis. Int. Arch. Allergy Appl. Immunol., 66, 1–12PubMedCrossRefGoogle Scholar
  32. 32.
    Casali, P., Burastero, S.E., Nakamura, M., Inghirami, G. and Notkins, A.L. (1987). Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to Leu-1+ B-cell subset. Science, 236, 77–81PubMedCrossRefGoogle Scholar
  33. 33.
    Hardy, R.R., Hayakawa, K., Shimizu, M., Yamasaki, K. and Kishimoto, T. (1987). Rheumatoid factor secretion from human Leu-1+ B-cells. Science, 236, 81–3PubMedCrossRefGoogle Scholar
  34. 34.
    Plater-Zyberk, C., Maini, R.N., Lam, K., Kennedy, T.D. and Janossy, G. (1985). A rheumatoid arthritis B cell subset expresses a phenotype similar to that in chronic lymphocytic leukemia. Arthr. Rheum., 28, 971–6CrossRefGoogle Scholar
  35. 35.
    Mossman, T.R., Cherwinski, H., Bard, M.W., Giedlin, M.A. and Coffman (1986). Two types of murine helper T-cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J. Immunol., 136, 2348–57Google Scholar
  36. 36.
    Cleveland, J.L., Rapp, U.R. and Farrar, W.L. (1987). Role of c-myc and other genes in interleukin-2 regulated CT6 lymphocytes and their malignant variants. J. Immunol., 138, 3495–504PubMedGoogle Scholar
  37. 37.
    Culpepper, J. and Lee, F. (1987). Glucocorticoid regulation of lymphokine production by murine T lymphocytes. In Webb, D.R. and Goeddel, D.V. (eds.) Molecular Cloning and Analysis of Lymphokines. pp. 275–89. (Orlando: Academic Press)Google Scholar
  38. 38.
    Chouaib, S., Welte K., Mortelsman, R. and Dupont, B. (1985). Prostaglandin E2 acts at two distinct pathways of T lymphocyte activation: inhibition of interleukin 2 production and down-regulation of transferrin receptor expression. J. Immunol., 135, 1172–9PubMedGoogle Scholar
  39. 39.
    Germain, R.N. and Malissen, B. (1986). Analysis of the expression and function of class II major histocompatibility complex-encoded molecules by DNA-mediated gene transfer. Annu. Rev. Immunol., 4, 281–315PubMedCrossRefGoogle Scholar
  40. 40.
    McDougal, J.S., Mawle, A., Cort, S.P., Nicholson, J.K.A., Cross, G.D., Scheppler-Campbell, J.A., Hicks, D. and Sligh, J. (1985). Cellular tropism of the human retrovirus HTLV/III/LAV I. Role of T-cell activation and expression of the T4 antigen. J. Immunol., 135, 3151–62PubMedGoogle Scholar
  41. 41.
    Burmester, G., Irani, Y.D., Kunkel, H., Winchester, R. (1981). Ia+ T-cells in synovial fluid and tissues of patients with rheumatoid arthritis. Arthr. Rheum., 24, 1370–6CrossRefGoogle Scholar
  42. 42.
    Reinherz, E.L., Kung, P.C. Pesando, J.M., Ritz, J., Goldstein, R. and Schlossman, S.F. (1979). Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression. J. Exp. Med., 150, 1472–82PubMedCrossRefGoogle Scholar
  43. 43.
    Veys, E.M., Hermanns, P., Goldstein, G., Kung, P., Schindler, J. and van Wauve, J. (1981). Determination of T lymphocyte subpopulations by monoclonal antibodies in rheumatoid arthritis. Influence of immunomodulating agents. Int. J. Immunopharmacol., 3, 313–9PubMedCrossRefGoogle Scholar
  44. 44.
    Forre, O., Thoen, J., Lea, T., Dobloug, J.H., Mellbye, O.J., Natvig, J.B., Pahle, J. and Solheim, B.G. (1982). In situ characterization of mononuclear cells in rheumatoid tissues, using monoclonal antibodies: no reduction of T8-positive cells or augmentation in T4-positive cells. Scand. J. Immunol., 16, 315–9PubMedCrossRefGoogle Scholar
  45. 45.
    Auron, P.E., Webb, A.C., Rosenwasser, J.J., Mucci, S.F., Rich, A., Wolff, S.M. and Dinarello, C.A. (1984). Nucleotide sequence of human monocyte interleukin-1 precursor cDNA. Proc. Natl Acad. Sci. USA, 81, 7907–11PubMedCrossRefGoogle Scholar
  46. 46.
    March, C.J., Mosley, B., Larsen, A., Cerretti, D.P., Braedt, G., Price, V., Gillis, S., Henney, C.S., Kronheim, S.R., Grabstein, K., Conlon, P.J., Hopp, T.P. and Cosman, D. (1985). Cloning, sequence, and expression of two distinct human interleukin-1 (IL-1) cDNAs. Nature, 315, 641–7PubMedCrossRefGoogle Scholar
  47. 47.
    Gubler, V., Chua, A.O., Stern, A.S., Hellmann, C.P., Vitek, M.P., Dechiara, T.M., Benjamin, W.R., Collier, K.J., Dukovitch, M., Familletti, P.C., Fielder-Nagy, C., Jensen, J., Kaffka, K., Kibian, P.L., Stremlo, D., Wittreich, B.H., Woehle, D., Mizel, S.B. and Lomedico, P.T. (1986). Recombinant human interleukin la: purification and biological characterization. J. Immunol., 136, 2492–7PubMedGoogle Scholar
  48. 48.
    Dower, S.K., Kronheim, S.R., March, C.J., Conlon, P.J., Hoff, T.P., Gillis, S. and Urdal, D. (1985). Detection and characterization of high affinity plasma membrane receptors for interleukin 1. J. Exp. Med., 162, 501–15PubMedCrossRefGoogle Scholar
  49. 49.
    Kenney, J.S., Masada, M.P., Eugui, E.M., De Lustro, B., Mulkins, M.A. and Allison, A.C. (1987). Monoclonal antibodies to human recombinant interleukin iβ: quantitation of IL-lβ and inhibition of biological activity. J. Immunol., 138, 4236–242PubMedGoogle Scholar
  50. 50.
    Bayne, E.K., Rupp, E.A., Limjuco, G., Chin, J. and Schmidt, J.A. (1986). Immunocyto-chemical detection of interleukin 1 within stimulated human monocytes. J. Exp. Med., 163, 1267–80PubMedCrossRefGoogle Scholar
  51. 51.
    Fontana, A., Hengartner, H., Weber, E., Fehr, K., Grob, P.K. and Cohen, G. (1982). Interleukin-1 activity in the synovial fluid of patients with rheumatoid arthritis. Rheumatol Int., 2, 49–53PubMedCrossRefGoogle Scholar
  52. 52.
    Wood, D.D., Ihrie, E.J., Dinarello, C.A. and Cohen, P.L. (1983). Isolation of an interleukin-1-like factor from human joint effusions. Arthr. Rheum., 26, 975–83CrossRefGoogle Scholar
  53. 53.
    Gaston, J.S.H., Strober, S., Solovera, J.J., Gaudow, D., Lane, N., Schurman, D., Hoppe, R.T., Chen, R.G, Eugui, E.M., Vaughan, J.H. and Allison, A.C. (1987). Dissection of the mechanisms of immune injury in rheumatoid arthritis using total lymphoid irradiation. Arthr. Rheum. (In press)Google Scholar
  54. 54.
    Gery, I. and Lepe-Zuniga, J.L. (1984). Interleukin 1: uniqueness of its production and spectrum of activities. Lymphokines, 9, 109–25Google Scholar
  55. 55.
    Di Giovine, F.S., Malawista, S.E., Nuki, G. and Duff, G.W. (1987). Interleukin 1 (IL-1) as a mediator of crystal arthritis. Stimulation of T-cell and synovial fibroblast mitogenesis by urate crystal-induced IL-1. J. Immunol., 138, 3213–8PubMedGoogle Scholar
  56. 56.
    Oppenheim, J.J., Togawa, A., Chedid, L. and Naizel, S. (1980). Components of mycobacteria and muramyl dipeptide with adjuvant activity induce lymphocyte-activating factor. Cell Immunol., 50, 71–81PubMedCrossRefGoogle Scholar
  57. 57.
    Habicht, G.S., Beck, G., Benach, J.L., Coleman, J.L. and Leichtling, K.D. (1985). Lyme disease spirochetes induce human and murine interleukin 1 production. J. Immunol., 134, 3147–54PubMedGoogle Scholar
  58. 58.
    Waters, R.V., Terrell, T. and Jones, G.H. (1986). Uveitis induction in the rabbit by muramyl dipeptides. Infect. Immun., 51, 816–25PubMedGoogle Scholar
  59. 59.
    Chou, Y.K., Sherwood, T. and Virella, G. (1985). Erythrocyte bound immune complexes trigger the release of interleukin-1 from human monocytes. Cell Immunol., 91, 308–14PubMedCrossRefGoogle Scholar
  60. 60.
    Nardella, F.A., Dayer, J.-M., Roelke, M, Krane, S.M. and Mannik, M. (1983). Self-associating IgG rheumatoid factors stimulate monocytes to release prostaglandins and mononuclear cell factor that stimulates collagenase and prostaglandin production by synovial cells. Rheumatol. Int., 3, 183–6PubMedCrossRefGoogle Scholar
  61. 61.
    Fair, A.G., Kiely, J.-M. and Unanue, E.A. (1979). Macrophage-T-cell interactions involving Listeria monocytogenes: role of the H2 gene-complex. J. Immunol., 122, 2395–404Google Scholar
  62. 62.
    Moore, R.N., Oppenheim, J.J., Farrar, J.J., Carter, CS. Jr., Waheed, A. and Shadduck, R.K. (1980). Production of LAF (IL-1) by macrophages activated with colony-stimulating factors. J. Immunol., 125, 1302–5PubMedGoogle Scholar
  63. 63.
    Arenzana-Seisdedos, F., Virelizier, J.-L. and Fiers, W. (1985). Interferons as macrophage-activating factors. III. Preferential effects of interferon-γ on the interleukin 1 secretory potential of fresh or aged human monocytes. J. Immunol., 134, 2444–8PubMedGoogle Scholar
  64. 64.
    Bevilacqua, M.P., Pober, J.S., Wheeler, M.E., Cotran, R.S. and Gimbrone, M.A. Jr. (1985). Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes and related leukocyte cell lines. J. Clin. Invest., 76, 2003–11PubMedCrossRefGoogle Scholar
  65. 65.
    Cavender, D.E., Haskard, D.O., Joseph, B. and Ziff, M. (1986). Interleukin 1 increases the binding of human B and T lymphocytes to endothelial cell monolayers. J. Immunol., 136, 203–7PubMedGoogle Scholar
  66. 66.
    Dayer, J.-M. and Demczuk, S. (1984). Cytokines and other mediators in rheumatoid arthritis. Springer Semin. Immunopathol., 7, 387–413PubMedCrossRefGoogle Scholar
  67. 67.
    Rossi, V., Brevario, F., Ghezzi, P., Dejana, E. and Mantovani, A. (1985). Prostacyclin synthesis induced in vascular cells by interleukin-1. Science, 229, 174–6PubMedCrossRefGoogle Scholar
  68. 68.
    Schnyder, J., Payne, T. and Dinarello, C.A. (1987). Human monocyte or recombinant interleukin 1’s are specific for the secretion of a metalloproteinase from chondrocytes. J. Immunol., 138, 496–503PubMedGoogle Scholar
  69. 69.
    Smith, R.L., Allison, A.C. and Schurman, D.J. (1987). Inhibition of interleukin-1 (IL-1) induced articular cartilage degradation by actinomycin D and cycloheximide. J. Orthopaed. Res. (In press)Google Scholar
  70. 70.
    Fell, H.B. and Jubb, R.W. (1977). The effect of synovial tissue on the breakdown of articular cartilage in culture. Arthr. Rheum., 20, 1359–71CrossRefGoogle Scholar
  71. 71.
    Saklatvala, J., Sarsfield, S.J. and Townsend, Y. (1985). Pig interleukin 1. Purification of two immunologically different leukocyte proteins that cause cartilage resorption, lymphocyte activation and fever. J. Exp. Med., 162, 1208–20PubMedCrossRefGoogle Scholar
  72. 72.
    Gowen, M., Wood, D.D., Ihrie, E.J., McGuire, M.K.B, and Russell, R.G.G. (1983). An interleukin-1-like factor stimulates bone resorption in vitro. Nature, 306, 378–80PubMedCrossRefGoogle Scholar
  73. 73.
    Stashenko, P., Dewhirst, F.E., Peros, W.J., Kent, R. and Ago, J.M. (1987). Synergistic interactions between interleukin-1, tumour necrosis factor, and lymphotoxin in bone resorption. J. Immunol., 138, 1464–8PubMedGoogle Scholar
  74. 74.
    Shore, A., Jaglal, S. and Keystone, E.C. (1986). Enhanced interleukin-1 generation by monocytes is temporally linked to an early event in the onset or exacerbation of rheumatoid arthritis. Clin. Exp. Immunol., 65, 293–302PubMedGoogle Scholar
  75. 75.
    Danis, V.A., March, L.M., Nelson, D.S. and Brooks, P.M. (1987). Interleukin-1 secretion by peripheral blood monocytes and synovial macrophages from patients with rheumatoid arthritis. J. Rheumatol, 14, 33–9PubMedGoogle Scholar
  76. 76.
    Pennick, D., Yang, G., Gemmell, L. and Lee, F. (1987). Control of hemopoiesis by a bone marrow stromal cell clone: lipopolysaccharide- and interleukin-1-inducible production of colony-stimulating factors. Blood, 69, 682–91Google Scholar
  77. 77.
    Schooley, J.C., Kullgren, B. and Allison, A.C. (1987). Inhibition of interleukin 1 of the action of erythropoietin on erythroid precursors and its possible role in the pathogenesis of hypoplastic anaemias. Br. J. Haematol, 67 Google Scholar
  78. 78.
    Lee, S.W., Tsou, A.-P., Chan, H., Thomas, J., Petrie, K., Eugui, E.M. and Allison, A.C. (1987). Glucocorticoids selectively inhibit the transcription of interleukin-1 genes and decrease the stability of IL-1β mRNA. Proc. Natl Acad. Sci. USA (In press)Google Scholar
  79. 79.
    Wevers, M.D., Rennard, S.I., Hance, A.J., Bitteman, P.B. and Crystal, R.G. (1984). Normal human macrophages obtained by bronchoalveolar lavage have a limited capacity to release interleukin-1. J. Clin. Invest., 74, 2208–18CrossRefGoogle Scholar
  80. 80.
    Egeland, T. and Lund, H. (1987). Immunoregulating lymphokines in rheumatoid joints. I. Search for interleukin-2 in synovial fluid. Scand. J. Immunol., 25, 101–6PubMedCrossRefGoogle Scholar
  81. 81.
    Husby, G. and Williams, R.C. Jr. (1985). Immunohistochemical studies of interleukin-2 and γ-interferon in rheumatoid arthritis. Arthr. Rheum., 28, 174–81CrossRefGoogle Scholar
  82. 82.
    Combe, B., Pope, R.M., Fischbach, M., Darnell, B., Baron, S. and Talal, N. (1985). Interleukin-2 in rheumatoid arthritis: production and response to interleukin-2 in rheumatoid synovial fluid, synovial tissue and peripheral blood. Clin. Exp. Immunol., 59, 520–8PubMedGoogle Scholar
  83. 83.
    Miossec, P., Kisiwado, T. and Ziff, M. (1987). Inhibitor of interleukin-2 in rheumatoid synovial fluid. Arthr. Rheum., 30, 121–9CrossRefGoogle Scholar
  84. 84.
    Lotz, M., Tsoucas, C.D., Fong, S., Dinarello, C.A., Carson, D.A. and Vaughan, J.H. (1986). Release of lymphokines after infection with Epstein-Barr virus in vitro. II. A monocyte-dependent inhibitor of interleukin-2 and interferon-gamma in rheumatoid arthritis. J. Immunol., 136, 3643–8PubMedGoogle Scholar
  85. 85.
    McKenna, R.M., Ofosu-Apprah, W. and Warrington, R.J. (1986). Interleukin 2 production and responsiveness in active and inactive rheumatoid arthritis. J. Rheumatol., 13, 28–32PubMedGoogle Scholar
  86. 86.
    Preble, O.T., Black, R.J., Friedman, R.M., Klippel, J.H. and Vilcek, J. (1982). Systemic lupus erythematosus: presence in human serum of an unusual acid-labile leukocyte interferon. Science, 216, 329–41CrossRefGoogle Scholar
  87. 87.
    Malaise, M.G. and Franchimont, P. (1987). Defective in vitro γ-interferon production in rheumatoid arthritis. Arthr. Rheum., 30, 230–331CrossRefGoogle Scholar
  88. 88.
    Hasler, F., Bluestein, H.G., Zwaifler, N.J. and Epstein, L.B. (1983). Analysis of the defects responsible for the impaired regulation of EBV-induced B-cell proliferation by rheumatoid arthritis lymphocytes. II. Role of monocytes and the increased sensitivity of rheumatoid arthritis lymphocytes to prostaglandin E. J. Immunol., 131, 768–72Google Scholar
  89. 89.
    Paul, W.E. and Ohara, J. (1987). B-cell stimulatory factor-1/interleukin 4. Annu. Rev. Immunol., 5, 429–59PubMedCrossRefGoogle Scholar
  90. 90.
    Hirano, T., Taga, T., Yasukawa, K., Nakajima, K., Nakano, N., Takatsuki, T., Shimizu, M., Murashima, A., Tsunasokawa, S., Sakiyama, F. and Kishimoto, T. (1987). Human B-cell differentiation factor defined by an anti-peptide antibody and its role in autoantibody production. Proc. Natl. Acad. Sci. USA, 84, 228–31PubMedCrossRefGoogle Scholar
  91. 91.
    Sehgal P.B., May, L.T., Tamm, I. and Vilček, J. (1987). Human β2-interferon and B-cell differentiation factor BSF-2 are identical. Science, 235, 731–2PubMedCrossRefGoogle Scholar
  92. 92.
    Klaus, G.C.B, and Havrylowicz, C.M. (1984). Activation and proliferation signals in mouse B cells. II. Evidence for activation (Go to G1) signals differing in sensitivity to cyclosporine. Eur. J. Immunol., 14, 250–4PubMedCrossRefGoogle Scholar
  93. 93.
    Varey, A.-M., Champion, B.R. and Cooke, A. (1986). Cyclosporine affects the function of antigen-presenting cells. Immunology, 57, 111–4PubMedGoogle Scholar
  94. 94.
    Yamamoto, K.R. (1985). Steroid receptor regulated transcription of specific genes and gene networks. Annu. Rev. Genet., 19, 209–15PubMedCrossRefGoogle Scholar
  95. 95.
    Flower, R.J. and Blackwell, G.J. (1979). Anti-inflammatory steroids induce synthesis of a phospholipase-A2 inhibitor which prevents prostaglandin generation. Nature, 278, 456–9PubMedCrossRefGoogle Scholar
  96. 96.
    Hirata, F., Schiffman, E., Venkatsubramanian, K., Solomon, D. and Axelrod, J. (1980). A phospholipase A2 inhibiting protein in rabbit neutrophils induced by glucocorticoids. Proc. Natl Acad. Sci. USA, 77, 2533–6PubMedCrossRefGoogle Scholar
  97. 97.
    Wallner, B.P., Mattaliano, R.J., Hessian, C., Cate, R.L., Tizard, R., Sinclair, L.K., Foeller, C., Chow, E.P., Browning, J.L., Ramchandran, K.L. and Pepinsky, R.B. (1986). Cloning and expression of human lipocortin, a phospholipase A2 inhibitor with potential antiinflammatory activity. Nature, 320, 72–5CrossRefGoogle Scholar
  98. 98.
    Saris, C.J., Tack, B.F., Kristensen, T., Glenny, J.R. Jr. and Hunter, T. (1986). The cDNA sequence for the protein-tyrosine kinase substrate p36 (calpatin 1 heavy chain) reveals a multidomain protein with internal repeats. Cell, 46, 201–12PubMedCrossRefGoogle Scholar
  99. 99.
    Davidson, F.F., Dennis, E.A., Powell, M. and Glenney, J.R. Jr. (1987). Inhibition of phospholipase A2 by ‘lipocortins’ and calpactins. An effect of binding to substrate phospholipids. J. Biol. Chem., 262, 1698–705PubMedGoogle Scholar
  100. 100.
    Snyder, D.S. and Unanue, E.R. (1982). Corticosteroids inhibit murine macrophage Ia expression and interleukin 1 production. J. Immunol., 129, 1803–5PubMedGoogle Scholar
  101. 101.
    Brinckerhoff, C.E., Plecinska, I.M., Sheldon, L.A. and O’Connor, G.T. (1986). Half life of synovial cell collagenase mRNA is modulated by phorbol myristate acetate but not by all-trans-rekinoic acid or dexamethasone. Biochemistry, 25, 6378–84PubMedCrossRefGoogle Scholar
  102. 102.
    Leizer, T., Clarris, B.J., Ash, P.E., van Damme, J., Saklatvala, J. and Hamilton, J.A. (1987). Interleukin-1β and interleukin-1α stimulate synovial cells. Arthr. Rheum., 30, 562–6CrossRefGoogle Scholar
  103. 103.
    Medcalf, R.L., Richards, R.I., Crawford, R.J. and Hamilton, J.A. (1986). Suppression of urokinase-type plasminogen activator mRNA levels in human fibrosarcoma cells and synovial fibroblasts by anti-inflammatory glucocorticoids. EMBO J., 5, 2217–22PubMedGoogle Scholar
  104. 104.
    Mitchell, M.D., Carr, B.R., Mason, J.L and Simpson, G.R. (1982). Prostaglandin biosynthesis in the human fetal adrenal gland: regulation by glucocorticosteroids. Proc. Natl Acad. Sci. USA, 79, 7547–51PubMedCrossRefGoogle Scholar
  105. 105.
    Crutchley, D.J., Ryan, U.S. and Ryan, J.W. (1985). Glucocorticoid modulation of prostacyclin production in cultured bovine pulmonary endothelial cells. J. Rheum. Exp. Eher., 233, 650–5Google Scholar
  106. 106.
    Hill, M.R., Smith, R.D. and McCallum, R.E. (1986). Interleukin 1: a regulatory role in glucocorticoid-regulated hepatic metabolism. J. Immunol., 137, 858–62PubMedGoogle Scholar
  107. 107.
    Mulkins, M. and Allison, A.C. (1987). Recombinant human interleukin-1 inhibits the induction by dexamethasone of alkaline phosphatase activity in murine capillary endothelial cells. J. Cell Physiol. (In press)Google Scholar
  108. 108.
    Bradley, L.M. and Mishell, R.I. (1982). Differential effects of glucocorticosteroids on the functions of subpopulations of helper T lymphocytes. Eur. J. Immunol., 12, 91–4PubMedCrossRefGoogle Scholar
  109. 109.
    Paavonen, T. (1985). Glucocorticoids enhance the in vitro Ig synthesis of pokeweed mitogen-stimulated human B-cells by inhibiting the suppressive effect of T8+ T cells. Scand. J. Immunol., 21, 63–71PubMedCrossRefGoogle Scholar
  110. 110.
    Cockayne, D., Sterling, K.M. Jr., Shull, S., Mintz, K.P., Illeyne, S. and Cutroneo, K.R. (1986). Glucocorticoids decrease the synthesis of type 1 procollagen RNAs. Biochemistry, 25, 3202–9PubMedCrossRefGoogle Scholar
  111. 111.
    Forestier, J. (1922). The treatment of rheumatoid arthritis with gold salts injection. Lancet, 1, 2235–7Google Scholar
  112. 112.
    Empire Rheumatism Council (1961). Gold therapy in rheumatoid arthritis: final report of a multicenter controlled trial. Ann. Rheum. Dis., 21, 315–33CrossRefGoogle Scholar
  113. 113.
    Lipsky, P. and Ziff, M. (1977). Inhibition of antigen- and mitogen-induced human lymphocyte proliferation by gold compounds. J. Clin. Invest., 59, 455–66PubMedCrossRefGoogle Scholar
  114. 114.
    Lipsky, P.E. (1981). Modulation of human antibody production in vitro by D-pencillamine and CuSO4: inhibition of helper T-cell function. J. Rheumatol., 9, (Suppl. 7), 69–73Google Scholar
  115. 115.
    Hunneyball, I.M., Crossley, M.J. and Spowage, M. (1986). Pharmacological studies of antigen-induced arthritis in Balb/c mice. II. The effects of second-line antirheumatic drugs and cytotoxic agents on the histopathological changes. Agents Actions, 18, 394–400PubMedCrossRefGoogle Scholar
  116. 116.
    Paska, W., McDonald, K.J. and Croft, M. (1986). Studies on type II collagen induced arthritis in mice. Agents Actions, 18, 413–20PubMedCrossRefGoogle Scholar
  117. 117.
    Vernon-Roberts, B., Dore, J.L., Jessop, J.D. and Henderson, W.J. (1976). Selective concentration and localization of gold in macrophages of synovial and other tissues during and after chrysotherapy in rheumatoid patients. Ann. Rheum. Dis., 35, 477–86PubMedCrossRefGoogle Scholar
  118. 118.
    Vernon-Roberts, B. (1979). Action of gold salts on the inflammatory response and inflammatory cell function. J. Rheumatol., 6 (suppl. 5), 120–9Google Scholar
  119. 119.
    Hamilton, J.A. and Williams, N. (1985). In vitro inhibition of myelopoiesis by gold salts and D-penicillamine. J. Rhematol., 12, 892–6Google Scholar
  120. 120.
    Hamilton, J.A. and Williams, N. (1987). Effects of auranofin and other antirheumatic drugs on human myelopoiesis in vitro. J. Rheumatol., 14, 216–20PubMedGoogle Scholar
  121. 121.
    Waters, R.V. and Allison, A.C. (1987). Gold salts inhibit proliferation of promonocytic cells and accelerate their differentiation. J. Rheumatol. (Submitted)Google Scholar
  122. 122.
    Vaughan, J.H., Fosi, R.I., Abresch, R.J., Tsoukas, CD., Curd, J.G. and Carson, P.A. (1984). Thoracic duct drainage in rheumatoid arthritis. Clin. Exp. Immunol., 58, 645–53PubMedGoogle Scholar
  123. 123.
    Ueo, T., Tanaka, S., Tominasa, Y., Osawa, H. and Sakurami, T. (1979). The effect of thoracic duct drainage on lymphocyte dynamics and clinical symptoms in patients with rheumatoid arthritis. Arthr. Rheum., 22, 1405–12CrossRefGoogle Scholar
  124. 124.
    Bucy, R.P. (1986). Alloantigen-specific suppressor T-cells are not inhibited by cyclosporin A but do require IL-2 for activation. J. Immunol., 137, 809–13PubMedGoogle Scholar
  125. 125.
    Damle, N.K., Childs, A.L. and Doyle, L.V. (1987). Immunoregulatory T lymphocytes in man. Soluble antigen-specific suppressor-inducer T lymphocytes are derived from the CD4+ CD45 P80+ subpopulation. J. Immunol., 139, 1501–8PubMedGoogle Scholar
  126. 126.
    Harris, E.D. (1986). Recent insights into the pathogenesis of the proliferative lesion in rheumatoid arthritis. Arthr. Rheum., 19, 68–72CrossRefGoogle Scholar
  127. 127.
    Mitchell, R.L., Zakas, L., Schreiber, R.D. and Verna, I. (1985). Rapid induction of the expression of the proto-oncogene fos during human monocytic differentiation. Cell, 40, 209–17PubMedCrossRefGoogle Scholar

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© MTP Press Limited 1988

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  • A. C. Allison

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