Skip to main content
SpringerLink
Log in

Konventionelle Basistherapie der rheumatoiden Arthritis

Wirkungen in und außerhalb der Zelle

Conventional basis therapy of rheumatoid arthritis

Effects within and outside cells

  • Leitthema
  • Published:
Zeitschrift für Rheumatologie Aims and scope Submit manuscript

Zusammenfassung

Konventionelle Basistherapeutika sind in der Regel empirisch in die Therapie der rheumatoiden Arthritis und anderer entzündlich rheumatischer Erkrankungen eingeführt worden. Ihr Wirkmechanismus ist häufig nur unzulänglich bekannt. In der Regel haben die konventionellen Basistherapeutika mehr als einen Angriffspunkt im Zellstoffwechsel. Weniger ausgeprägt, aber ebenfalls belegt sind direkte Wirkungen im Extrazellulärraum und an der Zellmembran.

Abstract

Conventional disease-modifying antirheumatic drugs (DMARDs) were formerly introduced into the treatment of rheumatoid arthritis and other rheumatic disorders on an empirical basis. In many cases their mode of action is only partially understood but as a rule of thumb they act on more than one point within the cellular metabolism. Less often they exert biological effects in the extracellular space or on the cell membrane.

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

Literatur

  1. Akahoshi T, Namai R, Sekiyama N et al (1997) Rapid induction of neutrophil apoptosis by sulfasalazine: implications of reactive oxygen species in the apoptotic process. J Leukoc Biol 62:817–826

    PubMed  CAS  Google Scholar 

  2. Belsky YP, Ivanova AN, Danilets MG et al (2011) Study of anti-inflammatory action of aurothiomalate, an inhibitor of NF-κB. Bull Exp Biol Med 151:190–193

    Article  PubMed  CAS  Google Scholar 

  3. Breedveld FC, Dayer JM (2000) Leflunomide: mode of action in the treatment of rheumatoid arthritis. Ann Rheum Dis 59:841–849

    Article  PubMed  CAS  Google Scholar 

  4. Burmester GR (2001) Molecular mechanisms of action of gold in treatment of rheumatoid arthritis – an update. Z Rheumatol 60:167–173

    Article  PubMed  CAS  Google Scholar 

  5. Cao WW, Kao PN, Chao AC et al (1995) Mechanism of the antiproliferative action of leflunomide. A77 1726, the active metabolite of leflunomide, does not block T-cell receptor-mediated signal transduction but its antiproliferative effects are antagonized by pyrimidine nucleosides. J Heart Lung Transplant 14:1016–1030

    PubMed  CAS  Google Scholar 

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

    PubMed  Google Scholar 

  7. Czock D, Keller F, Rasche FM, Haussler U (2005) Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet 44:61–98

    Article  PubMed  CAS  Google Scholar 

  8. Dimitrijevic M, Bartlett RR (1996) Leflunomide, a novel immunomodulating drug, inhibits homotypic adhesion of peripheral blood and synovial fluid mononuclear cells in rheumatoid arthritis. Inflamm Res 45:550–556

    Article  PubMed  CAS  Google Scholar 

  9. Fiehn C (2010) Methotrexate transport mechanisms: the basis for targeted drug delivery and ss-folate-receptor-specific treatment. Clin Exp Rheumatol 28:40–45

    Google Scholar 

  10. Fox RI (1993) Mechanism of action of hydroxychloroquine as an antirheumatic drug. Semin Arthritis Rheum 23:82–91

    Article  PubMed  CAS  Google Scholar 

  11. Gheorghe KR, Korotkova M, Catrina AI et al (2009) Expression of 5-lipoxygenase and 15-lipoxygenase in rheumatoid arthritis synovium and effects of intraarticular glucocorticoids. Arthritis Res Ther 11:R83

    Article  PubMed  Google Scholar 

  12. Goldman FD, Gilman AL, Hollenback C et al (2000) Hydroxychloroquine inhibits calcium signals in T cells: a new mechanism to explain its immunomodulatory properties. Blood 95:3460–3466

    PubMed  CAS  Google Scholar 

  13. Gossye V, Elewaut D, Bougarne N et al (2009) Differential mechanism of NF-kappaB inhibition by two glucocorticoid receptor modulators in rheumatoid arthritis synovial fibroblasts. Arthritis Rheum 60:3241–3250

    Article  PubMed  CAS  Google Scholar 

  14. Hirohata S, Ohshima N, Yanagida T, Aramaki K (2002) Regulation of human B cell function by sulfasalazine and its metabolites. Int Immunopharmacol 2:631–640

    Article  PubMed  CAS  Google Scholar 

  15. Imai F, Suzuki T, Ishibashi T et al (1994) Effect of sulfasalazine on B cell hyperactivity in patients with rheumatoid arthritis. J Rheumatol 21:612–615

    PubMed  CAS  Google Scholar 

  16. Kremer JM (1985) Longterm methotrexate therapy in rheumatoid arthritis: a review. J Rheumatol Suppl 12(Suppl 12):25–28

    PubMed  Google Scholar 

  17. Kuznik A, Bencina M, Svajger U et al (2011) Mechanism of endosomal TLR inhibition by antimalarial drugs and imidazoquinolines. J Immunol 186:4794–4804

    Article  PubMed  CAS  Google Scholar 

  18. Manenschijn L, Akker EL van den, Lamberts SW, Rossum EF van (2009) Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann N Y Acad Sci 1179:179–198

    Article  PubMed  CAS  Google Scholar 

  19. Meng XW, Feller JM, Ziegler JB et al (1997) Induction of apoptosis in peripheral blood lymphocytes following treatment in vitro with hydroxychloroquine. Arthritis Rheum 40:927–935

    Article  PubMed  CAS  Google Scholar 

  20. Montagna P, Soldano S, Brizzolara R et al (2010) Estrogens interfere with leflunomide modulation of cytokine production by human activated monocytes. Ann N Y Acad Sci 1193:30–35

    Article  PubMed  CAS  Google Scholar 

  21. Muhl H, Pfeilschifter J (2011) Pharmacogenetics and pharmacogenomics of methotrexate. Current status and novel aspects. Z Rheumatol 70:101–107

    Article  PubMed  CAS  Google Scholar 

  22. Nieminen R, Korhonen R, Moilanen T et al (2010) Aurothiomalate inhibits cyclooxygenase 2, matrix metalloproteinase 3, and interleukin-6 expression in chondrocytes by increasing MAPK phosphatase 1 expression and decreasing p38 phosphorylation: MAPK phosphatase 1 as a novel target for antirheumatic drugs. Arthritis Rheum 62:1650–1659

    Article  PubMed  CAS  Google Scholar 

  23. Pincus T, Ferraccioli G, Sokka T et al (2002) Evidence from clinical trials and long-term observational studies that disease-modifying anti-rheumatic drugs slow radiographic progression in rheumatoid arthritis: updating a 1983 review. Rheumatology (Oxford, England) 41:1346–1356

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

    Article  PubMed  CAS  Google Scholar 

  25. Rand JH, Wu XX, Quinn AS, Taatjes DJ (2010) The annexin A5-mediated pathogenic mechanism in the antiphospholipid syndrome: role in pregnancy losses and thrombosis. Lupus 19:460–469

    Article  PubMed  CAS  Google Scholar 

  26. Rau R (2000) Parenterales Gold. In: Rau R (Hrsg) Basistherapie der rheumatoiden Arthritis. Uni-Med, Bremen, S 146–169

  27. Rodenburg RJ, Ganga A, Lent PL van et al (2000) The antiinflammatory drug sulfasalazine inhibits tumor necrosis factor alpha expression in macrophages by inducing apoptosis. Arthritis Rheum 43:1941–1950

    Article  PubMed  CAS  Google Scholar 

  28. Spies CM, Cutolo M, Straub RH et al (2011) Prednisone chronotherapy. Clin Exp Rheumatol 29:42–45

    Google Scholar 

  29. Stenson WF, Mehta J, Spilberg I (1984) Sulfasalazine inhibition of binding of N-formyl-methionyl-leucyl-phenylalanine (FMLP) to its receptor on human neutrophils. Biochem Pharmacol 33:407–412

    Article  PubMed  CAS  Google Scholar 

  30. Strehl C, Gaber T, Lowenberg M et al (2011) Origin and functional activity of the membrane-bound glucocorticoid receptor. Arthritis Rheum 63:3779–3788

    Article  PubMed  CAS  Google Scholar 

  31. Borne BE van den, Dijkmans BA, Rooij HH de et al (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 

  32. Volin MV, Harlow LA, Woods JM et al (1999) Treatment with sulfasalazine or sulfapyridine, but not 5-aminosalicyclic acid, inhibits basic fibroblast growth factor-induced endothelial cell chemotaxis. Arthritis Rheum 42:1927–1935

    Article  PubMed  CAS  Google Scholar 

  33. Wahl C, Liptay S, Adler G, Schmid RM (1998) Sulfasalazine: a potent and specific inhibitor of nuclear factor kappa B. J Clin Invest 101:1163–1174

    Article  PubMed  CAS  Google Scholar 

  34. Wang ZY, Morinobu A, Kawano S et al (2002) Gold sodium thiomalate suppresses the differentiation and function of human dendritic cells from peripheral blood monocytes. Clin Exp Rheumatol 20:683–688

    PubMed  CAS  Google Scholar 

  35. Wittenberg HR, Kleemeyer K, Peskar BM, Peskar BA (1991) Effect of sulfasalazine and its metabolites on prostaglandin and leukotriene liberation from human synovial tissue. Wien Klin Wochenschr 103:34–39

    PubMed  CAS  Google Scholar 

  36. Wu XX, Guller S, Rand JH (2011) Hydroxychloroquine reduces binding of antiphospholipid antibodies to syncytiotrophoblasts and restores annexin A5 expression. Am J Obstet Gynecol 205:576 e577–514

    PubMed  Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Department für Innere Medizin, Klinik für Innere Medizin II, Universitätsklinikum Halle, Ernst-Grube-Str. 40, 06097, Halle (Saale), Deutschland

    G. Keyßer

Authors
  1. G. Keyßer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Keyßer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Keyßer, G. Konventionelle Basistherapie der rheumatoiden Arthritis. Z. Rheumatol. 71, 468–472 (2012). https://doi.org/10.1007/s00393-011-0878-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-011-0878-3

Schlüsselwörter

Keywords

Search

Navigation