Rheumatology International

, Volume 25, Issue 2, pp 108–113

Lack of evidence for inhibition of angiogenesis as a central mechanism of the antiarthritic effect of methotrexate


    • Medizinische Klinik und Poliklinik VUniversität Heidelberg
  • Andreas Wunder
    • Department of Radiochemistry and RadiopharmacologyGerman Cancer Research Center
  • Stefan Krienke
    • Department of Internal Medicine VUniversity of Heidelberg
  • Regina Max
    • Department of Internal Medicine VUniversity of Heidelberg
  • Anthony D. Ho
    • Department of Internal Medicine VUniversity of Heidelberg
  • Thomas Moehler
    • Department of Internal Medicine VUniversity of Heidelberg
Original Article

DOI: 10.1007/s00296-003-0408-y

Cite this article as:
Fiehn, C., Wunder, A., Krienke, S. et al. Rheumatol Int (2005) 25: 108. doi:10.1007/s00296-003-0408-y



The aim of this study was to investigate whether methotrexate (MTX) has an antiangiogenic effect and whether this property plays a role in the control of rheumatoid arthritis (RA).


A human placenta angiogenesis assay was used to examine the antiangiogenic effects of MTX in vitro. In addition, DBA/1 mice were used to compare the antiarthritic effect of MTX in collagen-induced arthritis (CIA) and its antiangiogenic effect in a murine in vivo matrigel model for angiogenesis.


The spreading of microvessels from placental vessel fragments was not significantly inhibited by MTX. Treatment with MTX reduced significantly the incidence of CIA in DBA/1 mice in a dose-dependent manner. However, treatment with the same doses of MTX did not significantly reduce vessel growth in subcutaneous depots of bFGF-enriched matrigel.


These data support the hypothesis that inhibition of angiogenesis does not significantly contribute to the antiarthritic effect of MTX seen in patients and animal models for RA. Therefore, the combination of MTX with antiangiogenic drugs appears to be a rational strategy in the treatment of RA.


AngiogenesisEndothelial cellsMethotrexateRheumatoid arthritis

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© Springer-Verlag 2003