Definition: Given a context passage, generate a question from the passage such that its answer is shortest continous span from the passage.
Input: Excessive neointima formation often occurs after arterial injury. Interleukin-1 (IL-1) is a potent pleiotropic cytokine that has been shown to regulate neointimal proliferation. We investigated the effects of the IL-1 modulator gevokizumab in a rat carotid denudation model. 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 50mg/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-1 and gevokizumab on human umbilical vein endothelial cells (HUVEC) and rat smooth muscle cells. We found that carotid IMT, in the proximal part of the denuded artery at day 28, was decreased by gevokizumab 1mg/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 1mg/kg dose also improved endothelial regrowth. No effect was observed with gevokizumab 10 or 50mg/kg. Gevokizumab also decreased the inflammatory effect of IL-1 in invitro cell experiments and protected HUVECs from IL-1's deleterious effects on cell migration, apoptosis and proliferation. A single administration of gevokizumab 1mg/kg improves endothelial regrowth and reduces neointima formation in rats following carotid denudation, at least in part through its beneficial effects on endothelial cells.
