Ibuprofen inhibits pyrogen-dependent expression of VCAM-1 and ICAM-1 on human endothelial cells

Life Sci. 1996;58(23):2167-81. doi: 10.1016/0024-3205(96)00210-x.


Leukocyte adhesion and transmigration through the endothelial cell (EC) layer plays a crucial role in inflammation. IL-1 alpha and TNF alpha increase EC-adhesiveness for leukocytes by stimulating surface expression of ICAM-1 (intercellular adhesion molecule 1, CD54), VCAM-1 (vascular cell adhesion molecule 1, CD106) and E-selectin (CD62E). In this study, the effects of ibuprofen on IL-1 alpha and TNF alpha-induced expression of ICAM-1, VCAM-1 and E-selectin on cultured human umbilical vein EC (HUVEC) were analyzed. Exposure to IL-1 alpha or TNF alpha resulted in an increased expression of VCAM-1, ICAM-1, and E-selectin. Ibuprofen was identified as a potent inhibitor of IL-1 alpha and TNF alpha-induced surface expression of VCAM-1 and a less potent inhibitor of pyrogen-induced expression of ICAM-1, whereas no effect on E-selectin was found. The effects of ibuprofen on VCAM-1 expression were dose-dependent (IC50 [IL-1 alpha]: 0.5 mM; IC50 [TNF alpha]: 0.5 mM) and time-dependent with maximum responses observed after 18 h. Moreover, ibuprofen abrogated pyrogen-dependent adhesion of leukocytes to HUVEC. Ibuprofen also inhibited VCAM-1 mRNA expression in pyrogen activated EC. VCAM-1-downregulation on EC by ibuprofen may contribute to the anti-inflammatory actions of the drug.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Adhesion
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cytokines / pharmacology
  • DNA Primers / chemistry
  • E-Selectin / metabolism
  • Endothelium, Vascular / metabolism*
  • Flow Cytometry
  • Gene Expression / drug effects
  • Humans
  • Ibuprofen / pharmacology*
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Interleukin-1 / metabolism
  • Leukocytes, Mononuclear / cytology
  • Molecular Sequence Data
  • Neutrophils / cytology
  • Pyrogens / pharmacology*
  • RNA, Messenger / genetics
  • Radioligand Assay
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism*


  • Cytokines
  • DNA Primers
  • E-Selectin
  • Interleukin-1
  • Pyrogens
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1
  • Ibuprofen