Cytokine therapy for arterial restenosis: inhibition of neointimal hyperplasia by gamma-interferon*1, *2

Inhibition of neointimal hyperplasia by gamma-interferon (gIFN) treatment was evaluated. Four groups of Sprague-Dawley rats (n = 72) weighing 500 g underwent endothelial injury of the carotid artery using the previously described Fogarty catheter technique. Group I (controls, n = 8) received one phosphate-buffered saline (PBS) injection 24h before injury and every 24h thereafter for a total of eight injections. Groups II (n = 8) and III (n = 8) received daily injections of 200,000 units of gIFN according to the same schedule except that group III did not receive the preoperative dose. Animals were killed on postoperative day 14. Histologic sections were analyzed morphometrically and immunohistochemically. Both gIFN groups had a statistically significant 50% reduction of the cross-sectional area of the neointimal hyperplasia compared with that of the controls (P < 0.01). Cell replication analysis of smooth muscle cells in the media and neointima revealed no statistically significant difference between controls and gIFN-treated groups. Group IV consisted of 48 rats that were treated with either PBS or gIFN on a schedule similar to that of groups I and II. Animals were killed at frequent time intervals during the first 7 days after injury. Their arteries were analyzed histologically and immunohistochemically. The results confirm previous findings that gIFN reduces the development of neointimal hyperplasia following arterial injury. The results also indicate that smooth muscle cells restore their proliferative activity by 7 days after discontinuation of gIFN treatment. It is proposed that efficacy of gIFN can be enhanced by lengthening the period of treatment.