Arterial inflammation in mice lacking the interleukin 1 receptor antagonist gene

Branch points and flexures in the high pressure arterial system have long b een recognized as sites of unusually high turbulence and consequent stress in humans are foci for atherosclerotic lesions, We show that mice that ape homozygous for a null mutation in the gene encoding an endogenous antiinfla mmatory cytokine, interleukin 1 receptor antagonist (IL-1ra), develop letha l arterial inflammation involving branch points and flexures of the aorta a nd its primary and secondary branches, We observe massive transmural infilt ration of neutrophils, macrophages, and CD4+ T cells. Animals appear to die from vessel wall collapse, stenosis, and organ infarction or from hemorrha ge from ruptured aneurysms. Heterozygotes do not die from arteritis within a year of birth but do develop small lesions, which suggests that a reduced level of IL-1ra is insufficient to fully control inflammation in arteries, Our results demonstrate a surprisingly specific role for IL-1ra in the con trol of:spontaneous inflammation in constitutively stressed artery walls, s uggesting that expression of IL-1 is likely to have a significant role in s ignaling artery wall damage.