OBJECTIVE: Excessive neointima formation often occurs after arterial injury. 
Interleukin-1β (IL-1β) is a potent pleiotropic cytokine that has been shown to 
regulate neointimal proliferation. We investigated the effects of the IL-1β 
modulator gevokizumab in a rat carotid denudation model.
METHODS: Sprague-Dawley rats were subjected to balloon denudation of the right 
carotid artery and were then randomized to receive a single subcutaneous 
infusion immediately after balloon injury of saline (control group, n = 13) or 
gevokizumab (gevokizumab groups, n = 15 in each group: 1, 10 and 50 mg/kg). We 
evaluated the treatment effects on carotid intima-media thickness (IMT) using 
ultrasonography, on endothelial regrowth using Evans Blue staining and on 
inflammatory response using histology. We also assessed the effects of IL-1β and 
gevokizumab on human umbilical vein endothelial cells (HUVEC) and rat smooth 
muscle cells.
RESULTS: We found that carotid IMT, in the proximal part of the denuded artery 
at day 28, was decreased by gevokizumab 1 mg/kg compared with controls. 
Neointima area and the intima/media area ratio were both reduced in the 
gevokizumab 1 mg/kg-treated group. Gevokizumab at the 1 mg/kg dose also improved 
endothelial regrowth. No effect was observed with gevokizumab 10 or 50 mg/kg. 
Gevokizumab also decreased the inflammatory effect of IL-1β in in vitro cell 
experiments and protected HUVECs from IL-1β's deleterious effects on cell 
migration, apoptosis and proliferation.
CONCLUSION: A single administration of gevokizumab 1 mg/kg improves endothelial 
regrowth and reduces neointima formation in rats following carotid denudation, 
at least in part through its beneficial effects on endothelial cells.