Differential effects of IFN-beta 1b on the proliferation of human vascularsmooth muscle and endothelial cells

The effect of human interferon (IFN)-beta 1b (Betaseron) on the proliferati on of cultured human vascular smooth muscle and endothelial cells was teste d in vitro. IFN-beta 1b inhibited thymidine incorporation and growth of pri mary cultures of human aortic and coronary artery smooth muscle in a concen tration-dependent manner. The same concentrations of IFN-beta 1b did not in hibit thymidine incorporation or growth of primary cultures of human aortic or coronary artery endothelial cells, IFN-beta 1b induced the expression o f MxA (an antiviral protein induced by type I IFNs) in both smooth muscle a nd endothelial cells, suggesting that both cell types express receptors for type I IFNs. The growth-inhibitory effect of IFN-beta 1b could be mimicked by commercially available human IFN-beta, but not by IFN-alpha 2 or IFN-al pha 8. The effect of IFN-beta 1b was species specific, as it did not inhibi t thymidine incorporation in aortic smooth muscle cells derived from pig, r abbit, rat, or mouse, The action of IFN-beta 1b on smooth muscle cells pers isted for at least 4 days following a 24 h preincubation with IFN-beta 1b H uman vascular smooth muscle cells treated with IFN-beta 1b did not release lactate dehydrogenase, nor did they show any morphologic change, suggesting that IFN-beta 1b was not toxic to the human vascular smooth muscle cells. IFN-beta 1b inhibited vascular smooth muscle growth while having no growth- inhibitory effect on endothelial cells obtained from the same blood vessel, making it a potential candidate for treating pathologic conditions where a bnormal vascular smooth muscle proliferation is implicated, such as resteno sis following balloon angioplasty or smooth muscle proliferation following vascular stenting.