Anti-vascular endothelial growth factor receptor-2 (Flk-1/KDR) antibody suppresses contact hypersensitivity

Exp Dermatol. 2004 Nov;13(11):671-81. doi: 10.1111/j.0906-6705.2004.00240.x.


The angiogenic mediator vascular endothelial growth factor (VEGF) and its receptors (VEGFRs) have been studied extensively in neoplastic disease and some inflammatory conditions. Contact hypersensitivity (CHS) is a prototypic Langerhans' cell-dependent, T-helper (Th) 1 cell-mediated inflammatory skin disease that is now also thought to involve angiogenic mediators. The purpose of our study was to examine the role of angiogenesis and VEGF in CHS. We demonstrated that VEGF production is up-regulated in murine skin after challenge with dinitrofluorobenzene. Administration of a monoclonal antibody directed against the VEGFR-2 (DC101) resulted in a 28.8% decrease in CHS response (P < 0.001). Examination of the DC101-treated mouse skin 24 h after challenge revealed decreases in dermal inflammatory cellular infiltrates and total vessel area. Furthermore, mRNA and protein of the Th1-type cytokine interferon (IFN)-gamma was significantly down-regulated in skin of DC101-treated animals 24 h after challenge. The results of the study demonstrate that VEGFR-2 blockade significantly reduces vascular enlargement and edema formation and effects IFN-gamma expression in the skin during challenge in CHS. Our findings suggest that DC101 could function by reducing inflammatory cell migration and hence IFN-gamma expression during the CHS response.

MeSH terms

  • Actins / metabolism
  • Animals
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / therapeutic use*
  • Dermatitis, Contact / immunology
  • Dermatitis, Contact / therapy*
  • Dinitrofluorobenzene / pharmacology
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Fluorescein-5-isothiocyanate / pharmacology
  • Immunohistochemistry
  • Inflammation
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / metabolism
  • Lectins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Microscopy, Confocal
  • Neovascularization, Pathologic
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Skin / metabolism
  • Th1 Cells / metabolism
  • Time Factors
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Vascular Endothelial Growth Factor Receptor-2 / antagonists & inhibitors
  • Vascular Endothelial Growth Factor Receptor-2 / immunology*


  • Actins
  • Antibodies, Monoclonal
  • Lectins
  • RNA, Messenger
  • Vascular Endothelial Growth Factor A
  • Interferon-gamma
  • Dinitrofluorobenzene
  • Vascular Endothelial Growth Factor Receptor-2
  • Fluorescein-5-isothiocyanate