Skip to main content

Advertisement

SpringerLink
Log in

Zytokine

Cytokines

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

Zusammenfassung

Zytokine sind körpereigene Substanzen, die von verschiedenen Zellen des Immunsystems im Rahmen der angeborenen und spezifischen Immunantwort freigesetzt werden. Sie sind an der Steuerung von Zellfunktionen, insbesondere von Entzündungsreaktionen, beteiligt. Während Zytokine unter physiologischen Bedingungen in der Regel nur temporär auf einen entsprechenden Stimulus hin gebildet und anschließend sehr rasch wieder abgebaut oder eliminiert werden, finden sich bei chronisch-entzündlichen Systemerkrankungen wie der rheumatoiden Arthritis persistierend erhöhte Spiegel von Zytokinen in den betroffenen Geweben. Ferner scheint es unabhängig vom jeweils vorliegenden Krankheitsbild bei Autoimmunerkrankungen eine gemeinsame, zytokinabhängige Endstrecke zu geben, in der einzelne Zytokine bestimmte Schrittmacherfunktionen in der Pathogenese innehaben.

Durch die gezielte Blockade von Zytokinen oder deren Funktion ist es gelungen, spezifisch in den Kreislauf autoimmuner Entzündungsreaktionen einzugreifen.

Die intensive Forschung über die letzten 2 Jahrzehnte identifizierte in diesem Zusammenhang zahlreiche therapeutische Zielstrukturen, von denen 2 Schlüsselzytokine (TNF-α und IL-1) in der Pharmakotherapie bereits erfolgreich genutzt werden. Mit der Modulation von IL-6 wird in absehbarer Zukunft ein weiteres, hochwirksames Therapieprinzip für Patienten mit rheumatoider Arthritis zur Verfügung stehen.

Abstract

Cytokine driven inflammation is a common feature in autoimmune diseases. Cytokines are needed under physiological conditions within the innate and adaptive immune systems to control infectious diseases and neoplastic disorders by regulation of the cell cycle and apoptosis. Cytokines can also be found in persistently increased concentrations in inflamed tissues within autoimmune diseases. Therefore, the modulation of cytokines seems to be a worthwhile therapeutic approach. With TNFα and Il-1, two key cytokines in rheumatoid arthritis have been identified. Their inhibition leads to a convincing clinical benefit. In the near future, inhibition of additional cytokines, such as Il-6 or Il-15, will likely open new beneficial strategies.

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

Abb. 1

Literatur

  1. Brennan FM, Chantry D, Jackson A et al. (1989) Inhibitory effect of TNF alpha antibodies on synovial cell interleukin-1 production in rheumatoid arthritis. Lancet 2: 244–247

    Article  PubMed  CAS  Google Scholar 

  2. Butler DM, Maini RN, Feldmann M, Brennan FM (1995) Modulation of proinflammatory cytokine release in rheumatoid synovial membrane cell cultures. Comparison of monoclonal anti TNF-alpha antibody with the interleukin-1 receptor antagonist. Eur Cytokine Netw 6: 225–230

    PubMed  CAS  Google Scholar 

  3. Haworth C, Brennan FM, Chantry D et al. (1991) Expression of granulocyte–macrophage colony-stimulating factor in rheumatoid arthritis: regulation by tumor necrosis factor-alpha. Eur J Immunol 21: 2575–2579

    Article  PubMed  CAS  Google Scholar 

  4. Katsikis PD, Chu CQ, Brennan FM et al. (1994) Immunoregulatory role of interleukin 10 in rheumatoid arthritis. J Exp Med 179: 1517–1527

    Article  PubMed  CAS  Google Scholar 

  5. Firestein GS, Xu WD, Townsend K et al. (1988) Cytokines in chronic inflammatory arthritis. I. Failure to detect T cell lymphokines (interleukin 2 and interleukin 3) and presence of macrophage colony-stimulating factor (CSF-1) and a novel mast cell growth factor in rheumatoid synovitis. J Exp Med 168: 1573–1586

    Article  PubMed  CAS  Google Scholar 

  6. Chomarat P, Vannier E, Dechanet J et al. (1995) Balance of IL-1 receptor antagonist/IL-1 beta in rheumatoid synovium and its regulation by IL-4 and IL-10. J Immunol 154: 1432–1439

    PubMed  CAS  Google Scholar 

  7. Joyce DA, Gibbons DP, Green P et al. (1994) Two inhibitors of pro-inflammatory cytokine release, interleukin-10 and interleukin-4, have contrasting effects on release of soluble p75 tumor necrosis factor receptor by cultured monocytes. Eur J Immunol 24: 2699–2705

    Article  PubMed  CAS  Google Scholar 

  8. Hermann JA, HallMA,Maini RN et al. (1998) Important immunoregulatory role of interleukin-11 in the inflammatory process in rheumatoid arthritis. Arthritis Rheum 41: 1388–1397

    Article  PubMed  CAS  Google Scholar 

  9. Woods JM, Katschke KJ Jr, Tokuhira M et al. (2000) Reduction of inflammatory cytokines and prostaglandin E2 by IL-13 gene therapy in rheumatoid arthritis synovium. J Immunol 165: 2755–2763

    PubMed  CAS  Google Scholar 

  10. Feldmann M, Brennan FM, Maini RN (1996) Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 14: 397–440

    Article  PubMed  CAS  Google Scholar 

  11. Vilcek J, Feldmann M (2004) Historical review: cytokines as therapeutics and targets of therapeutics. Trends Pharmacol Sci 25: 201–209

    Article  PubMed  CAS  Google Scholar 

  12. Feldmann M, Maini RN (2003) Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med 9: 1245–1250

    Article  PubMed  CAS  Google Scholar 

  13. Keane J, Gershon S, Wise RP et al. (2001) Tuberculosis associated with infliximab, a tumor necrosis factor alpha-neutralizing agent. N Engl J Med 345: 1098–1104

    Article  PubMed  CAS  Google Scholar 

  14. Scherer H, Burmester G (2004) Practical issues surrounding the use of biological therapies in patients with rheumatic diseases. Int J Adv Rheumatol 2: 2–8

    Google Scholar 

  15. Ekstrom K, Hjalgrim H, Brandt L et al. (2003) Risk of malignant lymphomas in patients with rheumatoid arthritis and in their first-degree relatives. Arthritis Rheum 48: 963–970

    Article  PubMed  Google Scholar 

  16. 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

    Article  PubMed  CAS  Google Scholar 

  17. Weinblatt ME, Keystone EC, Furst DE et al. (2003) Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial. Arthritis Rheum 48: 35–45 (Erratum in: Arthritis Rheum 2003, 48: 855; Arthritis Rheum 2004, 22: 144)

    Google Scholar 

  18. Moreland LW, Schiff MH, Baumgartner SW et al. (1999) Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial. Ann Intern Med 130: 478–486

    PubMed  CAS  Google Scholar 

  19. Weinblatt ME, Kremer JM, Bankhurst AD et al. (1999) A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate. N Engl J Med 340: 253–259

    Article  PubMed  CAS  Google Scholar 

  20. Klareskog L, Heijde D van der, Jager JP de et al. (2004) Therapeutic effect of the combination of etanercept and methotrexate compared with each treatment alone in patients with rheumatoid arthritis: double-blind randomised controlled trial. Lancet 363: 675–681

    Article  PubMed  CAS  Google Scholar 

  21. Horai R, Saijo S, Tanioka H et al. (2000) Development of chronic inflammatory arthropathy resembling rheumatoid arthritis in interleukin 1 receptor antagonist-deficient mice. J Exp Med 191: 313–320

    Article  PubMed  CAS  Google Scholar 

  22. Cohen S, Hurd E, Cush J et al. (2002) Treatment of rheumatoid arthritis with anakinra, a recombinant human interleukin-1 receptor antagonist, in combination with methotrexate: results of a twenty-four-week, multicenter, randomized, double-blind, placebo-controlled trial. Arthritis Rheum 46: 614–624

    Article  PubMed  CAS  Google Scholar 

  23. Nishimoto N, Kishimoto T (2006) Interleukin 6: from bench to bedside. Nat Clin Pract Rheumatol 2: 619–626; Review

    Article  PubMed  CAS  Google Scholar 

  24. McInnes IB, Gracie JA (2004) Interleukin-15: a new cytokine target for the treatment of inflammatory diseases. Curr Opin Pharmacol 4: 392–397

    Article  PubMed  CAS  Google Scholar 

  25. McInnes I, Martin R, Zimmerman-Gorska I et al. (2004) Safety and efficacy of human monoclonal antibody to IL-15 (AMG 714) in patients with rheumatoid arthritis (RA): results from a multicenter, randomized, double blind, placebo-controlled trial. Arthritis Rheum 50 (Suppl): S241

    Google Scholar 

Download references

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Schwerpunkt Rheumatologie/Klinische Immunologie, Medizinische Klinik mit Poliklinik II der Universität Würzburg, Klinikstraße 6, 97070, Würzburg, Deutschland

    M. Feuchtenberger, C. Kneitz & H.-P. Tony

Authors
  1. M. Feuchtenberger
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Kneitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H.-P. Tony
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Feuchtenberger.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feuchtenberger, M., Kneitz, C. & Tony, HP. Zytokine. Z. Rheumatol. 66, 297–303 (2007). https://doi.org/10.1007/s00393-007-0176-2

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00393-007-0176-2

Schlüsselwörter

Keywords

Search

Navigation