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Molekulare Grundlagen der Behandlung rheumatischer Erkrankungen

  • Chapter
Molekularmedizinische Grundlagen von rheumatischen Erkrankungen

Part of the book series: Molekulare Medizin ((MOLMED))

Zusammenfassung

Da die Pathogenese der chronischen Arthritiden und Autoimmunopathien, wie sie in diesem Buch dargestellt sind, nicht vollkommen geklärt ist, existiert auch kein kausaler Therapieansatz. Dennoch sind viele Prozesse, die auf molekularer Ebene zur Initiierung und/oder Perpetuierung der chronischen Entzündungsreaktionen führen, bekannt und akzeptiert. Da aber auch hier der Stellenwert der wichtigsten zu neutralisierenden proinflammatorischen Komponenten im gesamten Entzündungsgeschehen bei der jeweiligen Erkrankung unbekannt ist, zielen die geläufigen, so genannten Basistherapeutika (oder disease-modifying anti-rheumatic drugs, DMARD) auf eine ganze Reihe von entzündungsfördernden Mechanismen. Einzige Ausnahme sind hier die Immunbiologika, alien voran die Tumornekrosefaktor α (TNF-α) oder Interleukin-1 (IL-1) neutralisierenden Antikörper und Konstrukte, die spezifisch ihr Zielantigen erkennen und entweder hemmen oder durch Bindung an Membranmoleküle über nachgeordnete Signalketten die Zielzelle in ihrer Funktion alterieren.

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Literatur

  • Adams DH, Wang LF, Neuberger JM, Elias E (1990) Inhibition of leukocyte chemotaxis by immunosuppressive agents. Specific inhibition of lymphocyte chemotaxis by cyclosporine. Transplantation 50:845–850

    PubMed  CAS  Google Scholar 

  • Alarcon GS, Schrohenloher RE, Bartolucci AA, Ward JR, Williams HJ, Koopman WJ (1990) Suppression of rheumatoid factor production by methotrexate in patients with rheumatoid arthritis. Evidence for differential influences of therapy and clinical status on IgM and IgA rheumatoid factor expression. Arthritis Rheum 33:1156–1161

    PubMed  CAS  Google Scholar 

  • Andersen PA, West SG, O’Dell JR, Via CS, Claypool RG, Kotzin BL (1985) Weekly pulse methotrexate in rheumatoid arthritis. Clinical and immunologic effects in a randomized, double-blind study. Ann Intern Med 103:489–496

    PubMed  CAS  Google Scholar 

  • Asako H, Wolf RE, Granger DN (1993) Leukocyte adherence in rat mesenteric venules: effects of adenosine and methotrexate. Gastroenterology 104:31–37

    PubMed  CAS  Google Scholar 

  • Awumey EM, Moonga BS, Sodam BR et al. (1999) Molecular and functional evidence for calcineurin-A alpha and beta isoforms in the osteoclast: novel insights into cyclosporin A action on bone resorption. Biochem Biophys Res Commun 254:248–252

    PubMed  CAS  Google Scholar 

  • Baggott JE, Vaughn WH, Hudson BB (1986) Inhibition of 5-aminoimidazole-4-carboxamide ribotide transformylase, adenosine deaminase and 5′-adenylate deaminase by polyglutamates of methotrexate and oxidized folates and by 5-aminoimidazole-4-carboxamide riboside and ribotide. Biochem J 236:193–200

    PubMed  CAS  Google Scholar 

  • Barrera P, Haagsma CJ, Boerbooms AM et al. (1995) Effect of methotrexate alone or in combination with sulphasalazine on the production and circulating concentrations of cytokines and their antagonists. Longitudinal evaluation in patients with rheumatoid arthritis. Br J Rheumatol 34:747–755

    PubMed  CAS  Google Scholar 

  • Barrera P, Boerbooms AM, Putte LB van de, Meer JW van der (1996) Effects of antirheumatic agents on cytokines. Semin Arthritis Rheum 25:234–253

    PubMed  CAS  Google Scholar 

  • Bird HA (1995) Sulphasalazine, sulphapyridine or 5-aminosalicyclic acid — which is the active moiety in rheumatoid arthritis. Br J Rheumatol [Suppl 2] 34:16–19

    Google Scholar 

  • Boers M (1999) The case for corticosteroids in the treatment of early rheumatoid arthritis. Rheumatology 38:95–97

    PubMed  CAS  Google Scholar 

  • Bondeson J, Sundler R (1995) Auranofin inhibits the induction of interleukin-1beta and tumor necrosis factor alpha mRNA in macrophages. Biochem Pharmacol 50:1753–1759

    PubMed  CAS  Google Scholar 

  • Bono L, Cameron JS, Hicks JA (1999) The very long-term prognosis and complications of lupus nephritis and its treatment. QJM 92:211–218

    PubMed  CAS  Google Scholar 

  • Borne BE van den, Dijkmans BA, Rooij HH de, Cessie S le, Verweij CL (1997) Chloroquine and hydroxychloroquine equally affect tumor necrosis factor-alpha, interleukin 6, and interferon-gamma production by peripheral blood mononuclear cells. J Rheumatol 24:55–60

    PubMed  Google Scholar 

  • Borne BE van den, Landewe RB, Goei The HS et al. (1998) Combination therapy in recent onset rheumatoid arthritis: a randomized double blind trial of the addition of low dose cyclosporine to patients treated with low dose chloroquine. J Rheumatol 25:1493–1498

    PubMed  Google Scholar 

  • Bouma MG, Stad RK, Wildenberg FA van den, Buurman WA (1994) Differential regulatory effects of adenosine on cytokine release by activated human monocytes. J Immunol 153:4159–4168

    PubMed  CAS  Google Scholar 

  • Boyle DL, Sajjadi FG, Firestein GS (1996) Inhibition of synoviocyte collagenase gene expression by adenosine receptor stimulation. Arthritis Rheum 39:923–930

    PubMed  CAS  Google Scholar 

  • Brennan FM, Browne KA, Green PA, Jaspar JM, Maini RN, Feldmann M (1997) Reduction of serum matrix metalloproteinase 1 and matrix metalloproteinase 3 in rheumatoid arthritis patients following anti-tumour necrosis factor-alpha (cA2) therapy. Br J Rheumatol 36:643–650

    PubMed  CAS  Google Scholar 

  • Bresnihan B, Alvaro-Gracia JM, Cobby M et al. (1998) Treatment of rheumatoid arthritis with recombinant human interleukin-1 receptor antagonist. Arthritis Rheum 41:2196–2204

    PubMed  CAS  Google Scholar 

  • Bressolle F, Bologna C, Kinowski JM, Sany J, Combe B (1998) Effects of moderate renal insufficiency on pharmacokinetics of methotrexate in rheumatoid arthritis patients. Ann Rheum Dis 57:110–113

    PubMed  CAS  Google Scholar 

  • Burmester GR, Barthel HR (1996) Wirkmechanismen von Gold bei der Behandlung der rheumatoiden Arthritis. Z Rheumatol 55:299–306

    PubMed  CAS  Google Scholar 

  • Cannon GW, McCall S (1990) Inhibition of the passive transfer of adjuvant induced arthritis by gold sodium thiomalate. J Rheumatol 17:436–438

    PubMed  CAS  Google Scholar 

  • Carlsson KH, Monzel W, Jurna J (1988) Depression by morphine and non-opioid analgesic agents, metamizol (dipyrone), lysine acetylsalicylate, and paracetamol, of activity in rat thalamus neurons evoked by electrical stimulation of nociceptive afferents. Pain 32:313–326

    PubMed  CAS  Google Scholar 

  • Chabner BA, Allegra CJ, Curt GA et al. (1985) Polyglutamation of methotrexate. Is methotrexate a prodrug? J Clin Invest 76:907–912

    PubMed  CAS  Google Scholar 

  • Cherwinski HM, Cohn RG, Cheung P et al. (1995) The immunosuppressant leflunomide inhibits lymphocyte proliferation by inhibiting pyrimidine biosynthesis. J Pharmacol Exp Ther 275:1043–1049

    PubMed  CAS  Google Scholar 

  • Chong AS, Huang W, Liu W et al. (1999) In vivo activity of leflunomide: pharmacokinetic analyses and mechanism of immunosuppression. Transplantation 68:100–109

    PubMed  CAS  Google Scholar 

  • Connolly KM, Stecher VJ, Danis E, Pruden DJ, LaBrie T (1988) Alteration of interleukin-1 production and the acute phase response following medication of adjuvant arthritic rats with cyclosporin-A or methotrexate. Int J Immunopharmacol 10:717–728

    PubMed  CAS  Google Scholar 

  • Constatin A, Loubet-Lescoulie P, Lambert N, Coppin H, Mazieres B, Cantagrel A (1996) Cytokine expression assessed by competitive RT-PCR in rheumatoid arthritis: in vitro modulation by methotrexate. Arthritis Rheum [Suppl 9] 39: S126

    Google Scholar 

  • Corkill MM, Kirkham BW, Haskard DO, Barbatis C, Gibson T, Panayi GS (1991) Gold treatment of rheumatoid arthritis decreases synovial expression of the endothelial leukocyte adhesion receptor ELAM-1. J Rheumatol 18:1453–1460

    PubMed  CAS  Google Scholar 

  • Crilly A, McInnes IB, Capell HA, Madhok R (1994) The effect of azathioprine on serum levels of interleukin 6 and soluble interleukin 2 receptor. Scand J Rheumatol 23:87–91

    PubMed  CAS  Google Scholar 

  • Cronstein BN (1995) The antirheumatic agents sulphasalazine and methotrexate share an anti-inflammatory mechanism. Br J Rheumatol [Suppl 2] 34:30–32

    Google Scholar 

  • Cronstein BN (1996) Molecular therapeutics. Methotrexate and its mechanism of action. Arthritis Rheum 39:1951–1960

    PubMed  CAS  Google Scholar 

  • Cronstein BN, Rosenstein ED, Kramer SB, Weissmann G, Hirschhorn R (1985) Adenosine; a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. J Immunol 135:1366–1371

    PubMed  CAS  Google Scholar 

  • Cronstein BN, Levin RI, Belanoff J, Weissmann G, Hirschhorn R (1986) Adenosine: an endogenous inhibitor of neutrophil-mediated injury to endothelial cells. J Clin Invest 78:760–770

    PubMed  CAS  Google Scholar 

  • Cronstein BN, Eberle MA, Gruber HE, Levin RI (1991) Methotrexate inhibits neutrophil function by stimulating adenosine release from connective tissue cells. Proc Natl Acad Sci USA 88:2441–2445

    PubMed  CAS  Google Scholar 

  • Cronstein BN, Naime D, Ostad E (1993) The antiinflammatory mechanism of methotrexate. Increased adenosine release at inflamed sites diminishes leukocyte accumulation in an in vivo model of inflammation. J Clin Invest 92:2675–2682

    PubMed  CAS  Google Scholar 

  • Cronstein BN, Naime D, Firestein G (1995) The antiinflammatory effects of an adenosine kinase inhibitor are mediated by adenosine. Arthritis Rheum 38:1040–1045

    PubMed  CAS  Google Scholar 

  • Cunha FQ, Poole S, Lorenzetti BB, Ferreira SH (1992) The pivotal role of tumor necrosis factor alpha in the development of inflammatory hyperalgesia. Br J Pharmacol 107:660–664

    PubMed  CAS  Google Scholar 

  • Cuperus RA, Muijsers AO, Wever R (1985) Antiarthritic drugs containing thiol groups scavenge hypochlorite and inhibit its formation by myeloperoxidase from human leukocytes. A therapeutic mechanism of these drugs in rheumatoid arthritis? Arthritis Rheum 28:1228–1233

    PubMed  CAS  Google Scholar 

  • Cupps TR, Edgar LC, Fauci AS (1982) Suppression of human B lymphocyte function by cyclophosphamide. J Immunol 128:2453–2457

    PubMed  CAS  Google Scholar 

  • Czeuz R, Barnes P, Panayi GS (1990) Natural killer cells in the blood of patients with rheumatoid arthritis treated with azathioprine. Br J Rheumatol 29:284–287

    PubMed  CAS  Google Scholar 

  • Danis VA, Frank GM, Brooks PM (1991) The effect of slow-acting anti-rheumatic drugs (SAARDS) and combinations of SAARDS on monokine production in vitro. Drugs Exp Clin Res 17:549–554

    PubMed  CAS  Google Scholar 

  • Davis P, Johnston C, Miller C, Wong K (1983) Effects of gold compounds on the function of phagocytic cells. II. Inhibition of superoxide radical generation by tripeptide-activated polymorphonuclear leukocytes. Arthritis Rheum 26:82–86

    PubMed  CAS  Google Scholar 

  • Edelman J, Biggo DF, Tandy N, Russell AS (1984) Low dose methotrexate kinetics in arthritis. Clin Pharm Ther 35:382–386

    CAS  Google Scholar 

  • Ennis RS, Granda JL, Posner AS (1968) Effect of gold salts and other drugs on the release and activity of lysosomal hydrolases. Arthritis Rheum 11:756–764

    PubMed  CAS  Google Scholar 

  • Feehally J, Beattie TJ, Brenchley PE et al. (1984) Modulation of cellular immune function by cyclophosphamide in children with minimal-change nephropathy. N Engl J Med 310:415–420

    PubMed  CAS  Google Scholar 

  • Firestein GS, Boyle D, Bullough DA et al. (1994) Protective effect of an adenosine kinase inhibitor in septic shock. J Immunol 152:5853–5859

    PubMed  CAS  Google Scholar 

  • Firestein GS, Paine MM, Boyle DL (1994) Mechanisms of methotrexate action in rheumatoid arthritis: selective decrease in synovial collagenase gene expression. Arthritis Rheum 37:193–200

    PubMed  CAS  Google Scholar 

  • Firestein GS, Bullough DA, Erion MD et al. (1995) Inhibition of neutrophil adhesion by adenosine and an adenosine kinase inhibitor. The role of selectins. J Immunol 154:326–334

    PubMed  CAS  Google Scholar 

  • Flescher E, Bowlin TL, Ballester A, Houk R, Talal N (1989) Increased polyamines may downregulate interleukin 2 production in rheumatoid arthritis. J Clin Invest 83:1356–1362

    PubMed  CAS  Google Scholar 

  • Fox R (1996) Anti-malarial drugs: possible mechanisms of action in autoimmune disease and prospects for drug development. Lupus [Suppl 1] 5:S4–S10

    CAS  Google Scholar 

  • Fox RI, Kang HI (1993) Mechanisms of action of antimalarial drugs: inhibition of antigen processing and presentation. Lupus ]Suppl 1] 2:S9–12

    CAS  Google Scholar 

  • Furumitsu Y, Yukioka K, Kojima A et al. (1993) Levels of urinary polyamines in patients with rheumatoid arthritis. J Rheumatol 20:1661–1665

    PubMed  CAS  Google Scholar 

  • Gadangi P, Longaker M, Naime D et al. (1996) The anti-inflammatory mechanism of sulfasalazine is related to adenosine release at inflamed sites. J Immunol 156:1937–1941

    PubMed  CAS  Google Scholar 

  • Griem P, Takahashi K, Kalbacher H, Gleichmann E (1995) The antirheumatic drug disodium aurothiomalate inhibits CD4+ T cell recognition of peptides containing two or more cystein residues. J Immunol 155:1575–1587

    PubMed  CAS  Google Scholar 

  • Grünke M, Schiller M, Hieronymus T et al. (2000) Synergistic effects of combinations of established DMARDs and immunobiological drugs in vitro. Arthritis Rheum 43:S364

    Google Scholar 

  • Hall TJ, Jeker H, Nyugen H, Schaeublin M (1996) Gold salts inhibit osteoclastic bone resorption in vitro. Inflamm Res 45:230–233

    PubMed  CAS  Google Scholar 

  • Halloran PF (1996) Molecular mechanisms of new immunosuppressants. Clin Transplant 10:118–123

    PubMed  CAS  Google Scholar 

  • Handel ML, Sivertsen S, Watts CK, Day RO, Sutherland RL (1993) Comparative effects of gold on the interactions of transcription factors with DNA. Agents Actions Suppl 44:219–223

    PubMed  CAS  Google Scholar 

  • Hanly JG, Bresnihan B (1985) Reduction of peripheral blood lymphocytes in patients receiving gold therapy for rheumatoid arthritis. Ann Rheum Dis 44:299–301

    PubMed  CAS  Google Scholar 

  • Hanly JG, Hassan J, Whelan A, Feighery C, Bresnihan B (1986) Effects of gold therapy on the synthesis and quantity of serum and synovial fluid IgM, IgG, and IgA rheumatoid factors in rheumatoid arthritis patients. Arthritis Rheum 29:480–487

    PubMed  CAS  Google Scholar 

  • Harth M, McCain GA, Orange JF (1985) The effects of auranofin and gold sodium aurothiomalate on the chemoluminescent response of stimulated synovial tissue cells from patients with rheumatoid arthritis. J Rheumatol 12:881–884

    PubMed  CAS  Google Scholar 

  • Hashimoto K, Witehurst CE, Lipsky PE (1994) Synergistic inhibition of T cell proliferation by gold sodium thiomalate and auranofin. J Rheumatol 21:1020–1026

    PubMed  CAS  Google Scholar 

  • Higgs GA (1980) Arachidonic acid metabolism, pain and hyperalgesia: the mode of action of non-steroid mild analgesics. Br J Clin Pharmacol 10:233S–235S

    PubMed  Google Scholar 

  • Hirohata S, Lipsky PE (1994) Comparative inhibitory effects of bucillamine and D-penicillamine on the function of human B-cells and T-cells. Arthritis Rheum 37:942–950

    PubMed  CAS  Google Scholar 

  • Hirohata S, Yanagida T, Hashimoto H et al. (1997) Differential influences of gold sodium thiomalate and bucillamine on the generation of CD14+ monocyte-lineage cells from bone marrow of rheumatoid arthritis patients. Clin Immunol Immunopathol 84:290–295

    PubMed  CAS  Google Scholar 

  • Ho PP, Young AL, Southard GL (1978) Methyl ester of N-formylmethionyl-leucyl-phenylalanine: chemotactic responses of human blood monocytes and inhibition of gold compounds. Arthritis Rheum 21:133–136

    PubMed  CAS  Google Scholar 

  • Hodis HN, Quismorio FP, Wickham E, Blankenhorn DH (1993) The lipid, lipoprotein, and apolipoprotein effects of hydroxychloroquine in patients with systemic lupus erythematosus. J Rheumatol 20:661–665

    PubMed  CAS  Google Scholar 

  • Howard-Lock HE, Lock CJ, Mewa A, Kean WF (1986) D-Penicillamine: chemistry and clinical use in rheumatic disease. Semin Arthritis Rheum 15:261–281

    PubMed  CAS  Google Scholar 

  • Hu SK, Mitcho YL, Oronsky AL, Kerwar SS (1988) Studies on the effect of methotrexate on macrophage function. J Rheumatol 15:206–209

    PubMed  CAS  Google Scholar 

  • Ishitani K, Matsuura A, Honda H (1995) Auranofin inhibits calcium uptake into opsonized-zymosan-stimulated neutrophils obtained from rats. Inflamm Res 44:482–485

    PubMed  CAS  Google Scholar 

  • Joosten LA, Helsen MM, Loo FA van de, Berg WB van den (1996) Anticytokine treatment of established type II collagen-induced arthritis in DBA/1 mice. A comparative study using anti-TNF alpha, anti-IL-1 alpha/beta, and IL1Ra. Arthritis Rheum 39:797–809

    PubMed  CAS  Google Scholar 

  • Kalden-Nemeth D, Grebmeier J, Antoni C, Manger B, Wolf F, Kalden JR (1997) NMR monitoring of rheumatoid arthritis patients receiving anti-TNF-alpha monoclonal antibody therapy. Rheumatol Int 16:249–255

    PubMed  CAS  Google Scholar 

  • Karres I, Kremer JP, Dietl I, Steckholzer U, Jochum M, Ertel W (1998) Chloroquine inhibits proinflammatory cytokine release into human whole blood. Am J Physiol 274:R1058–1064

    PubMed  CAS  Google Scholar 

  • Kerstens PJ, Stolk JN, De Abreu RA, Lambooy LH, Putte LB van de, Boerbooms AA (1995) Azathioprine-related bone marrow toxicity and low activities of purine enzymes in patients with rheumatoid arthritis. Arthritis Rheum 38:42–45

    Google Scholar 

  • Kirwan JR, Russell AS (1998) Systemic glucocorticoid treatment in rheumatoid arthritis — a debate. Scand J Rheumatol 27:247–251

    PubMed  CAS  Google Scholar 

  • Koch AE, Burrows JC, Polverini PJ, Cho M, Leibovich SJ (1991) Thiol-containing compounds inhibit the production of monocyte/macrophage-derived angiogenic activity. Agents Actions 34:350–357

    PubMed  CAS  Google Scholar 

  • Kremer JM GJ, Streckfuss A, Kamen B (1986) Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates. Arthritis Rheum 29:832–835

    PubMed  CAS  Google Scholar 

  • Kremer JM, Caldwell JR, Cannon GW et al. (2000) The combination of leflunomide and methotrexate in patients with active rheumatoid arthritis who are failing on methotrexate treatment alone. Arthritis Rheum 43:S224

    Google Scholar 

  • Krynetski EY, Tai HL, Yates CR et al. (1996) Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanisms. Pharmacogenetics 6:279–290

    PubMed  CAS  Google Scholar 

  • Kuiper S, Joosten LA, Bendele AM et al. (1998) Different roles of tumour necrosis factor alpha and interleukin 1 in murine streptococcal cell wall arthritis. Cytokine 10:690–702

    PubMed  CAS  Google Scholar 

  • Lacki JK, Klama K, Mackiewicz SH, Mackiewicz U, Müller W (1995) Circulating interleukin 10 and interleukin-6 serum levels in rheumatoid arthritis patients treated with methotrexate or gold salts: preliminary report. Inflamm Res 44:24–26

    PubMed  CAS  Google Scholar 

  • Lacki JK, Leszczynski P, Mackiewicz SH (1996) Intravenous cyclophosphamide combined with methylprednisolone in the treatment of severe refractory rheumatoid arthritis: the effect on lymphocytes. J Invest Allergol Clin Immunol 6:232–236

    CAS  Google Scholar 

  • Laurindo IM, Mello SB, Cossermelli W (1995) Influence of low dose methotrexate on superoxide anion production by polymorphonuclear leukocytes from patients with rheumatoid arthritis. J Rheumatol 22:633–638

    PubMed  CAS  Google Scholar 

  • Le Moine O, Stordeur P, Schadene L et al. (1996) Adenosine enhances IL-10 secretion by human monocytes. J Immunol 156:4408–4414

    PubMed  Google Scholar 

  • Ledson MJ, Bucknall RC, Edwards SW (1992) Inhibition of neutrophil oxidant secretion by D-penicillamine: scavenging of H2O2 and HOCl. Ann Rheum Dis 51:321–325

    PubMed  CAS  Google Scholar 

  • Lewins EG, Cripps AW, Clancy RL, Major GA (1982) Penicillamine-induced immunosuppression: in vitro studies of inhibition of immunoglobulin synthesis. J Rheumatol 9:677–684

    PubMed  CAS  Google Scholar 

  • Lipsky PE (1984) Immunosuppression by D-penicillamine in vitro. Inhibition of human T lymphocyte proliferation by copper — or ceruloplasmin dependent generation of hydrogen peroxide and protection by monocytes. J Clin Invest 73:53–65

    PubMed  CAS  Google Scholar 

  • Lipsky PE, Ziff M (1980) Inhibition of human helper T cell function in vitro by D-penicillamine and CuSO4. J Clin Invest 65:1069–1076

    PubMed  CAS  Google Scholar 

  • Loetscher P, Dewald B, Baggiolini M, Seitz M (1994) Monocyte chemoattractant protein 1 and interleukin-8 production by rheumatoid synoviocytes: effects of anti-rheumatic drugs. Cytokine 6:162–170

    PubMed  CAS  Google Scholar 

  • Lorenz H-M (2000) Biological agents: a novel approach to the therapy of rheumatoid arthritis. Exp Opin Invest Drugs 9:1479–1490

    CAS  Google Scholar 

  • Lorenz H-M, Antoni C, Valerius T et al. (1996) In vivo blockade of TNF-alpha by i. v. infusion of a chimeric, monoclonal TNF-alpha antibody in patients with rheumatoid arthritis: short term cellular and molecular effects. J Immunol 156:1646–1653

    PubMed  CAS  Google Scholar 

  • Loudon JR (1988) Hydroxychloroquine and postoperative thromboembolism after total hip replacement. Am J Med 85:57–61

    PubMed  CAS  Google Scholar 

  • Madhok R, Wijelath E, Smith J, Watson J, Surrock RD, Capell HA (1991) Is the beneficial effect of sulfasalazine due to inhibition of synovial neovascularization? J Rheumatol 18:199–202

    PubMed  CAS  Google Scholar 

  • Maini R, St Clair EW, Breedveld F et al. (1999) Infliximab (chimeric anti-tumour necrosis factor alpha monoclonal antibody) versus placebo in rheumatoid arthritis patients receiving concomitant methotrexate: a randomised phase III trial. ATTRACT Study Group. Lancet 354:1932–1939

    PubMed  CAS  Google Scholar 

  • Manna SK, Mukhopadhyay A, Aggarwal BB (2000) Leflunomide suppresses TNF-induced cellular responses: effects on NF-kappaB, activator protein-1, c-Jun N-terminal protein kinase, and apoptosis. J Immunol 165:5962–5969

    PubMed  CAS  Google Scholar 

  • Martel-Pelletier J, McCollum R, Fujimoto N, Obata K, Cloutier JM, Pelletier JP (1994) Excess of metalloproteinases over tissue inhibitor of metalloproteinases may contribute to cartilage degradation in osteoarthritis and rheumatoid arthritis. Lab Invest 70:807–815

    PubMed  CAS  Google Scholar 

  • Matsubara T, Hirohata K (1988) Suppression of human fibroblast proliferation by D-penicillamine and copper sulfate in vitro. Arthritis Rheum 31:964–972

    PubMed  CAS  Google Scholar 

  • Matsubara T, Saura R, Hirohata K, Ziff M (1989) Inhibition of human endothelial cell proliferation in vitro and neovascularization in vivo by D-penicillamine. J Clin Invest 83:158–167

    PubMed  CAS  Google Scholar 

  • Merluzzi VJ, Kenney RE, Schmid FA, Choi YS, Faanes RB (1981) Recovery of the in vivo cytotoxic T-cell response in cyclophosphamide-treated mice by injection of mixedlymphocyte-culture supernatants. Cancer Res 41:3663–3665

    PubMed  CAS  Google Scholar 

  • Merrill JT, Shen C, Schreibman D et al. (1997) Adenosine Al receptor promotion of multinucleated giant cell formation by human monocytes: a mechanism for methotrexate-induced nodulosis in rheumatoid arthritis. Arthritis Rheum 40:1308–1315

    PubMed  CAS  Google Scholar 

  • Meyn RE, Stephens LC, Hunter NR, Milas L (1994) Induction of apoptosis in murine tumors by cyclophosphamide. Cancer Chemother Pharmacol 33:410–414

    PubMed  CAS  Google Scholar 

  • Middleton GD, McFarlin JE, Lipsky PE (1995) Hydroxychloroquine and pain thresholds. Arthritis Rheum 38:445–446

    PubMed  CAS  Google Scholar 

  • Mirmohammadsadegh A, Homey B, Abts HF, Kohrer K, Ruzicka T, Michel G (1998) Differential modulation of pro-and anti-inflammatory cytokine receptors by N-(4-trifluoromethylphenyl)-2-cyano-3-hydroxy-crotonic acidamide (A77 1726), the physiologically active metabolite of the novel immunomodulator leflunomide. Biochem Pharmacol 55:1523–1529

    PubMed  CAS  Google Scholar 

  • Morgan SL, Baggott JE, Vaughn WH et al. (1994) Supplementation with folic acid during methotrexate therapy for rheumatoid arthritis. A double-blind, placebo-controlled trial. Ann Intern Med 121

    Google Scholar 

  • Morrison E, Capell HA (1999) Corticosteroids in rheumatoid arthritis — the case against. Rheumatology 38:97–100

    PubMed  CAS  Google Scholar 

  • Mowat AG (1978) Neutrophil chemotaxis in rheumatoid arthritis. Effect of D-penicillamine, gold salts, and levamisole. Ann Rheum Dis 37:1–8

    PubMed  CAS  Google Scholar 

  • Müller-Ladner U, Roberts CR, Franklin BN et al. (1996) Gene transfer of the TNF-α receptor p55 into human synovial fibroblasts and implantation into the SCID mouse. Arthritis Rheum 39:S307

    Google Scholar 

  • Müller-Ladner U, Roberts CR, Franklin BN et al. (1997) Human IL-IRa gene transfer into human synovial fibroblasts is chondroprotective. J Immunol 158:3492–3498

    PubMed  Google Scholar 

  • Munro R, Capell HA (1997) Penicillamine. Br J Rheumatol 36:104–109

    PubMed  CAS  Google Scholar 

  • Munro R, Morrison E, McDonald AG, Hunter JA, Madhok R, Capell HA (1997) Effect of disease modifying agents on the lipid profiles of patients with rheumatoid arthritis. Ann Rheum Dis 56:374–377

    PubMed  CAS  Google Scholar 

  • Myles A (1985) Corticosteroid treatment in rheumatoid arthritis. Br J Rheumatol 24:125–127

    PubMed  CAS  Google Scholar 

  • Norga K, Grillet B, Masure S, Paemen L, Opdenakker G (1996) Human gelatinase B, a marker enzyme in rheumatoid arthritis, is inhibited by D-penicillamine: anti-rheumatic activity by protease inhibition. Clin Rheumatol 15:31–34

    PubMed  CAS  Google Scholar 

  • Nosal R, Jancinova V, Petrikova M (1995) Chloroquine inhibits stimulated platelets at the arachidonic acid pathway. Thromb Res 77:531–542

    PubMed  CAS  Google Scholar 

  • Odaka C, Mizuochi T (1999) Role of macrophage lysosomal enzymes in the degradation of nucleosomes of apoptotic cells. J Immunol 163:5346–5352

    PubMed  CAS  Google Scholar 

  • Ohshima S, Saeki Y, Mima T et al. (1996) Possible mechanism for the long-term efficacy of anti-TNF alpha antibody (cA2) therapy in RA. Arthritis Rheum [Suppl 9] 39:S242

    Google Scholar 

  • Ohshima S, Saeki Y, Mima T et al. (1999) Long-term follow-up of the changes in circulating cytokines, soluble cytokine receptors, and white blood cell subset counts in patients with rheumatoid arthritis (RA) after monoclonal anti-TNF alpha antibody therapy. J Clin Immunol 19:305–313

    PubMed  CAS  Google Scholar 

  • Olsen NJ, Jasin HE (1984) Decreased pokeweed mitogen-induced IgM and IgM rheumatoid factor synthesis in rheumatoid arthritis patients treated with gold sodium thiomalate or penicillamine. Arthritis Rheum 27:985–994

    PubMed  CAS  Google Scholar 

  • Olsen NJ, Callahan LF, Pincus T (1987) Immunologic studies of rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 30:481–488

    PubMed  CAS  Google Scholar 

  • Paleolog EM, Hunt M, Elliott MJ, Feldmann M, Maini RN, Woody JN (1996) Deactivation of vascular endothelium by monoclonal anti-tumor necrosis factor alpha antibody in rheumatoid arthritis. Arthritis Rheum 39:1082–1091

    PubMed  CAS  Google Scholar 

  • Paleolog EM, Young S, Stark AC, McCloskey RV, Feldmann M, Maini RN (1998) Modulation of angiogenic vascular endothelial growth factor by tumor necrosis factor α and interleukin-1 in rheumatoid arthritis. Arthritis Rheum 41:1258–1265

    PubMed  CAS  Google Scholar 

  • Parmely MJ, Zhou WW, Edwards CKd, Borcherding DR, Silverstein R, Morrison DC (1993) Adenosine and a related carbocyclic nucleoside analogue selectively inhibit tumor necrosis factor-alpha production and protect mice against endotoxin challenge. J Immunol 151:389–396

    PubMed  CAS  Google Scholar 

  • Penneys NS, Ziboh V, Gottlieb NL, Katz S (1974) Inhibition of prostaglandin synthesis and human epidermal enzymes by aurothiomalate in vitro: possible actions of gold in pemphigus. J Invest Dermatol 63:356–361

    PubMed  CAS  Google Scholar 

  • Quatraro A, Consoli G, Magno M et al. (1990) Hydroxychloroquine in decompensated, treatment-refractory noninsulin-dependent diabetes mellitus. A new job for an old drug? Ann Intern Med 112:678–681

    PubMed  CAS  Google Scholar 

  • Rahman P, Gladman DD, Urowitz MB, Yuen K, Hallett D, Bruce IN (1999) The cholesterol lowering effect of anti-malarial drugs is enhanced in patients with lupus taking corticosteroid drugs. J Rheumatol 26:325–330

    PubMed  CAS  Google Scholar 

  • Rains CP, Noble S, Faulds D (1995) Sulphasalazine. A review of its pharmacological properties and therapeutic efficacy in the treatment of rheumatoid arthritis. Drugs 50:137–156

    PubMed  CAS  Google Scholar 

  • Reinhold-Keller E, Beuge N, Latza U et al. (2000) An interdisciplinary approach to the care of patients with Wegener’s granulomatosis: long-term outcome in 155 patients. Arthritis Rheum 43:1021–1032

    PubMed  CAS  Google Scholar 

  • Remick DG, Nguyen DT, Eskandari MK, Strieter RM, Kunkel SL (1989) Cyclosporine A inhibits TNF production without decreasing TNF mRNA levels. Biochem Biophys Res Commun 161:551–555

    PubMed  CAS  Google Scholar 

  • Roberts DE, Curd JG (1990) Sulfonamides as anti-inflammatory agents in the treatment of Wegener’s granulomatosis. Arthritis Rheum 33:1590–1593

    PubMed  CAS  Google Scholar 

  • Roberts NA, Robinson PA (1985) Copper chelates of antirheumatic and anti-inflammatory agents: their superoxide dismutase-like activity and stability. Br J Rheumatol 24:128–136

    PubMed  CAS  Google Scholar 

  • Rodenburg RJT, Ganga A, Lent PLEM van, Putte LBA van de, Venrooij WJ van (2000) The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor a expression in macrophages by inducing apoptosis. Arthritis Rheum 43:1941–1950

    PubMed  CAS  Google Scholar 

  • Rosenblatt DS, Whitehead VM, Vera N, Pottier A, Dupont M, Vuchich MJ (1978) Prolonged inhibition of DNA synthesis associated with the accumulation of methotrexate polyglutamates by cultured human cells. Mol Pharmacol 14:1143–1147

    PubMed  CAS  Google Scholar 

  • Rosengren S, Bong GW, Firestein GS (1995) Anti-inflammatory effects of an adenosine kinase inhibitor. Decreased neutrophil accumulation and vascular leakage. J Immunol 154:5444–5451

    PubMed  CAS  Google Scholar 

  • Ruckemann K, Fairbanks LD, Carrey EA et al. (1998) Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J Biol Chem 273:21.682–21.692

    Google Scholar 

  • Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-alpha expression by adenosine: role of A3 adenosine receptors. J Immunol 156: 3435–3442

    PubMed  CAS  Google Scholar 

  • Schlaghecke R, Kornely E, Wollenhaupt J, Specker C (1992) Glucocorticoid receptors in rheumatoid arthritis. Arthritis Rheum 35:740–744

    PubMed  CAS  Google Scholar 

  • Schreiber SL, Crabtree GR (1992) The mechanism of action of cyclosporin A and FK506. Immunol Today 13:136–142

    PubMed  CAS  Google Scholar 

  • Schror K, Sauerland S, Kuhn A, Rosen R (1980) Different sensitivities of prostaglandin-cyclooxygenases in blood platelets and coronary arteries against non-steroidal antiinflammatory drugs. Naunyn Schmiedebergs Arch Pharmacol 313:69–76

    PubMed  CAS  Google Scholar 

  • Schultz DR, Volonakis JE, Arnold PI (1974) Inactivation of CI in rheumatoid synovial fluid, purified CI and CI esterase, by gold compounds. Clin Exp Immunol 17:395–400

    PubMed  CAS  Google Scholar 

  • Seitz M, Dewald B, Ceska M, Gerber N, Baggiolini M (1992) Interleukin-8 in inflammarory rheumatic diseases: synovial fluid levels, relation to rheumatoid factors, production by mononuclear cells, and effects of gold sodium thiomalate and methotrexate. Rheumatol Int 12:159–164

    PubMed  CAS  Google Scholar 

  • Seitz M, Loetscher P, Dewald B et al. (1995) Methotrexate action in rheumatoid arthritis: stimulation of cytokine inhibitor and inhibition of chemokine production by peripheral blood mononuclear cells. Br J Rheumatol 34:602–609

    PubMed  CAS  Google Scholar 

  • Seitz M, Loetscher P, Dewald B, Towbin H, Baggiolini M (1997) In vitro modulation of cytokine, cytokine inhibitor, and prostaglandin E release from blood mononuclear cells and synovial fibroblasts by antirheumatic drugs. J Rheumatol 24:1471–1476

    PubMed  CAS  Google Scholar 

  • Siemasko K, Chong AS, Jack HM, Gong H, Williams JW, Finnegan A (1998) Inhibition of JAK3 and STAT6 tyrosine phosphorylation by the immunosuppressive drug leflunomide leads to a block in IgGl production. J Immunol 160:1581–1588

    PubMed  CAS  Google Scholar 

  • Sinnett MJ, Groff GD, Raddatz DA, Franck WA, Bertino JSJ (1989) Methotrexate pharmacokinetics in patients with rheumatoid arthritis. J Rheumatol 16:745–748

    PubMed  CAS  Google Scholar 

  • Smedegard G, Bjork J (1995) Sulphasalazine: mechanism of action in rheumatoid arthritis. Br J Rheumatol [Suppl 2] 34:7–15

    PubMed  Google Scholar 

  • Smialowicz RJ, Luebke RW, Riddle MM, Rogers RR, Rowe DG (1985) Evaluation of the immunotoxic potential of chlordecone with comparison to cyclophosphamide. J Toxicol Environ Health 15:561–574

    PubMed  CAS  Google Scholar 

  • Smith CS, Ortega G, Parker L, Shearer WT (1994) Cyclosporine A blocks induction of tumor necrosis factor-alpha in human B-lymphocytes. Biochem Biophys Res Commun 204:383–390

    PubMed  CAS  Google Scholar 

  • Soden M, Rooney M, Whelan A, Feighery C, Bresnihan B (1991) Immunohistological analysis of the synovial membrane: search for predictors of the clinical course in rheumatoid arthritis. Ann Rheum Dis 50:673–676

    PubMed  CAS  Google Scholar 

  • Spisani S, Fabbri E, Rizzuti O et al. (2000) Inhibition of neutrophil responses by cyclosporine. Ann Rheum Dis 59:122

    Google Scholar 

  • Stevens C, Lipman M, Fabry S, Moscovitch-Lopatin M et al. (1995) 5-Aminosalicylic acid abrogates Tcell proliferation by blocking interleukin-2 production in peripheral blood mononuclear cells. J Pharmacol Exp Ther 272:399–406

    PubMed  CAS  Google Scholar 

  • Tak PP, Taylor PC, Breedveld FC et al. (1996) Decrease in cellularity and expression of adhesion molecules by antitumor necrosis factor alpha monoclonal antibody treatment in patients with rheumatoid arthritis. Arthritis Rheum 39:1077–1081

    PubMed  CAS  Google Scholar 

  • Taylor PC, Peters AM, Paleolog E et al. (2000) Reduction of chemokine levels and leukocyte traffic to joints by tumor necrosis factor alpha blockade in patients with rheumatoid arthritis. Arthritis Rheum 43:38–47

    PubMed  CAS  Google Scholar 

  • Ten Berge RJ, Schellekens PT, Surachno S, The TH, Ten Veen JH, Wilmink JM (1981) The influence of therapy with azathioprine and prednisone on the immune system of kidney transplant recipients. Clin Immunol Immunopathol 21:20–32

    PubMed  Google Scholar 

  • Tett S, Cutler D, Day R (1990) Antimalarials in rheumatic diseases. Baillieres Clin Rheumatol 4:467–489

    PubMed  CAS  Google Scholar 

  • Thomas R, Carroll GJ (1993) Reduction of leukocyte and interleukin-1 beta concentrations in the synovial fluid of rheumatoid arthritis patients treated with methotrexate. Arthritis Rheum 36:1244–1252

    PubMed  CAS  Google Scholar 

  • Tirri G, La Montagna G, Salaffi F et al. (1997) Combination therapy with cyclosporin and hydroxychloroquine in early active severe rheumatoid arthritis. Arthritis Rheum 40:S97

    Google Scholar 

  • Tomono M, Toyoshima K, Ito M, Amano H (1996) Calcineurin is essential for DNA synthesis in Swiss 3T3 fibroblasts. Biochem J 317:675–680

    PubMed  CAS  Google Scholar 

  • Tschesche H, Blaser J, Kleine T et al. (1994) Inhibition of matrix metalloproteinases in rheumatoid arthritis and the crystallographic binding mode of a peptide inhibitor. Ann N Y Acad Sci 732:400–402

    PubMed  CAS  Google Scholar 

  • Vane JR, Botting RM (1998) Mechanism of action of nonsteroidal anti-inflammatory drugs. Am J Med 104:2S–8S

    PubMed  CAS  Google Scholar 

  • Wahl C, Liptay S, Adler G, Schmid RM (1998) Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest 101:1163–1167

    PubMed  CAS  Google Scholar 

  • Wallace DJ, Metzger AL, Stecher VJ, Turnbull BA, Kern PA (1990) Cholesterol-lowering effect of hydroxychloroquine in patients with rheumatic disease: reversal of deleterious effects of steroids on lipids. Am J Med 89:322–326

    PubMed  CAS  Google Scholar 

  • Walters MT, Smith JL, Moore K, Evans PR, Cawley MI (1987) An investigation of the action of disease modifying antirheumatic drugs on the rheumatoid synovial membrane: reduction in T lymphocyte subpopulations and HLA-DP and DQ antigen expression after gold or penicillamine therapy. Ann Rheum Dis 46:7–16

    PubMed  CAS  Google Scholar 

  • Watt I, Cobby M (1996) Recombinant human IL-1 receptor antagonist (rhIL-1ra) reduces the rate of joint erosion in rheumatoid arthritis (RA). Arthritis Rheum [Suppl 9] 39:S123

    Google Scholar 

  • Weber CK, Liptay S, Wirth T, Adler G, Schmid RM (2000) Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology 119:1209–1218

    PubMed  CAS  Google Scholar 

  • Weinblatt ME, Kremer JM, Coblyn JS et al. (1999) Pharmacokinetics, safety, and efficacy of combination treatment with methotrexate and leflunomide in patients with active rheumatoid arthritis. Arthritis Rheum 42:1322–1328

    PubMed  CAS  Google Scholar 

  • Weisman MH (1995) Corticosteroids in the treatment of rheumatologic diseases. Curr Opin Rheumatol 7:183–190

    PubMed  CAS  Google Scholar 

  • Willoughby DA, Moore AR, Colville-Nash PR (2000) COX-1, COX-2, and COX-3 and the future treatment of chronic inflammatory disease. Lancet 355:646–648

    PubMed  CAS  Google Scholar 

  • Wolf G, Thaiss F, Stahl RA (1995) Cyclosporine stimulates expression of transforming growth factor-beta in renal cells. Possible mechanism of cyclosporines antiproliferative effects. Transplantation 60:237–241

    PubMed  CAS  Google Scholar 

  • Wolfe F, Hawley DJ, Cathey MA (1990) Termination of slow acting antirheumatic therapy in rheumatoid arthritis: a 14-year prospective evaluation of 1017 consecutive starts. J Rheumatol 17:994–1002

    PubMed  CAS  Google Scholar 

  • Yadav R, Misra R, Naik S (1997) In vitro effect of gold sodium thiomalate and methotrexate on tumor necrosis factor production in normal healthy individuals and patients with rheumatoid arthritis. Int J Immunopharmacol 19:111–114

    PubMed  CAS  Google Scholar 

  • Yamashita M, Niki H, Yamada M, Watanabe-Kobayashi M, Mue S, Ohuchi K (1997) Dual effects of auranofin on prostaglandin E2 production by rat peritoneal macrophages. Eur J Pharmacol 325:221–227

    PubMed  CAS  Google Scholar 

  • Yanni G, Nabil M, Farahat MR, Poston RN, Panayi GS (1994) Intramuscular gold decreases cytokine expression and macrophage numbers in the rheumatoid synovial membrane. Ann Rheum Dis 53:315–322

    PubMed  CAS  Google Scholar 

  • Yoon C-H, Cho M-L, Min S-Y et al. (2000) Cyclosporine A inhibits vascular endothelial growth factor production in cultured rheumatoid synovial fibroblasts. Ann Rheum Dis 59:188

    Google Scholar 

  • Yukioka K, Wakitani S, Yukioka M et al. (1992) Polyamine levels in synovial tissues and synovial fluids of patients with rheumatoid arthritis. J Rheumatol 19:689–692

    PubMed  CAS  Google Scholar 

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  1. Hanns-Martin Lorenz
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  1. Max-Delbrück-Centrum für Molekulare Medizin (MDC), Robert-Rössle-Straße 10, 13122, Berlin-Buch, Deutschland

    Detlev Ganten  & Klaus Ruckpaul  & 

  2. Center of Experimental Rheumatology, University Hospital, Gloriastraße 25, 8091, Zürich, Schweiz

    Steffen Gay

  3. Institut für Klinische Immunologie Medizinische Klinik III, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glückstraße 4a, 91054, Erlangen, Deutschland

    Jochen R. Kalden

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Lorenz, HM. (2003). Molekulare Grundlagen der Behandlung rheumatischer Erkrankungen. In: Ganten, D., Ruckpaul, K., Gay, S., Kalden, J.R. (eds) Molekularmedizinische Grundlagen von rheumatischen Erkrankungen. Molekulare Medizin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-55803-0_9

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