Role of inflammatory responses in initiation of atherosclerosis: effects of anti-inflammatory drugs on cuff-induced leukocyte accumulation and intimal thickening of rabbit carotid artery

Atherosclerosis. 1991 Nov;91(1-2):107-16. doi: 10.1016/0021-9150(91)90192-6.


Immediately after a cuff-sheathing of rabbit carotid artery, a large number of leukocytes adhered to injured endothelium then infiltrated into the media. These inflammatory responses were followed by an atherosclerotic change, intimal thickening, of the artery. A simultaneous injection of dexamethasone (10 mg/kg i.m.) inhibited the leukocyte accumulation by 74% when evaluated 18 h thereafter. Similarly, 39% inhibition was obtained with the same dose of FR110302, a potent 5-lipoxygenase inhibitor. On the other hand, the same dose of indomethacin, a cyclooxygenase inhibitor, had little effect on the leukocyte accumulation. The intimal thickening which was evaluated 3 weeks after the cuff-treatment was attenuated by a daily dose (10 mg/kg i.m.) of dexamethasone or FR110302 but not by one of indomethacin. The inhibition by the two former drugs were 91 and 58%, respectively. In vitro, the three drugs in concentrations up to 10 microM hardly affected endothelial adhesion of PMN which was induced by LPS or IL-1. Though 10 microM of FR110302 and indomethacin significantly decreased PMN chemotaxis induced by LTB4, the decreases were less than that at 10 microM dexamethasone. These results confirm a possible linkage between inflammation and atherosclerosis, and suggest that 5-lipoxygenase products contribute to the initiation and development of atherosclerosis.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Arteriosclerosis / pathology*
  • Arteriosclerosis / physiopathology
  • Carotid Arteries / pathology*
  • Carotid Arteries / ultrastructure
  • Cell Adhesion
  • Cell Movement
  • Dexamethasone / pharmacology
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / ultrastructure
  • Indomethacin / pharmacology
  • Inflammation / pathology
  • Male
  • Microscopy, Electron, Scanning
  • Naphthols / pharmacology
  • Neutrophils / pathology*
  • Neutrophils / physiology
  • Neutrophils / ultrastructure
  • Quinolines / pharmacology
  • Rabbits


  • Anti-Inflammatory Agents
  • Naphthols
  • Quinolines
  • FR 110302
  • Dexamethasone
  • Indomethacin