Chamberlain, Janet and Evans, David and King, Andrea and Dewberry, Rachael and Dower, Steven and Crossman, David and Francis, Sheila (2006) Interleukin-1beta and signaling of interleukin-1 in vascular wall and circulating cells modulates the extent of neointima formation in mice. American Journal of Pathology, 168 (4). pp. 1396-1403. ISSN 0002-9440
Full text not available from this repository.Abstract
Interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Here, we examined the role of IL-1 in arterial neointima formation. Carotid artery neointima was induced by ligation, and arteries were harvested 4 weeks after injury. The neointima/media of mice deficient in the IL-1 signaling receptor (IL-1R1−/−) was significantly reduced compared to IL-1R1+/+ controls (P < 0.01). IL-1R1+/+ mice receiving subcutaneous IL-1ra also had significantly reduced neointima/media compared with placebo (P < 0.05). IL-1β−/− mice had reduced neointima/media compared to wild-type (P < 0.05), whereas IL-1α−/− mice were no different from controls. Mice deficient in the P2X7 receptor (involved in IL-1 release) or caspase-1 (involved in IL-1 activation) did not differ in their response to carotid ligation compared to controls. To examine the site of IL-1 signaling, we generated chimeric mice. IL-1R1+/+ mice receiving IL-1R1−/− marrow and IL-1R1−/− mice receiving IL-1R1+/+ marrow both had significantly reduced neointima/media compared with IL-1R1+/+ to IL-1R1+/+ (P < 0.05) but had significantly greater neointima/media than IL-1R1−/− to IL-1R1−/− controls (P < 0.05). These data confirm the importance of IL-1β signaling in mediating arterial neointima formation and suggest the involvement of IL-1 signaling in both circulating and arterial wall cells. Furthermore, receptor antagonism may be a better therapeutic target than interruption of IL-1β processing or release.