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(Circulation. 2005;111:3135-3140.)
© 2005 American Heart Association, Inc.

Vascular Medicine

Elastic-Vessel Arteritis in Interleukin-1 Receptor Antagonist–Deficient Mice Involves Effector Th1 Cells and Requires Interleukin-1 Receptor

From the Division of Genomic Medicine, University of Sheffield, Sheffield, United Kingdom.

Correspondence to Martin Nicklin, University of Sheffield, Division of Genomic Medicine, Sir Henry Wellcome Laboratories for Medical Research, Medical School, Beech Hill Rd, Sheffield S10 2RX, United Kingdom. E-mail m.nicklin{at}shef.ac.uk

Received June 26, 2004; de novo received November 4, 2004; revision received January 19, 2005; accepted March 2, 2005.

Background— In mice that lack interleukin-1 receptor antagonist (IL-1ra), transmural inflammation of the elastic arteries develops at sites of turbulent flow. We described late histopathology previously. Here, we investigate the cellular events in nonlethal arteritis at the aortic root and compare them with Takayasu’s arteritis and giant cell arteritis.

Methods and Results— IL-1ra–deficient mice were inbred from the original stocks and from BALB/c backcrosses. Disease was ascertained histologically and immunohistologically postmortem at the aortic root. Onset appeared to be stochastic and was not detectably age dependent; in our local Sf3 strain, the half-time of onset was 52 days. Loss of the type I IL-1 receptor suppressed the arteritis. Microvascular activation, as determined by absence of strong E-selectin expression, was absent from preaffected vessels. In mildly affected cases, infiltration was adventitial. In severely affected animals, infiltrates appeared to be active in destroying elastin, but resynthesis of disorganized elastin occurred at closely adjacent sites. Infiltrates consisted predominantly of macrophages but were rich in CD4⁺–interferon-⁺ cells, which are likely to represent Th1 cells. Dendritic cells accumulated in lesional areas.

Conclusions— The arteritic phenotype of IL-1ra deficiency is mediated by the interleukin-1 receptor and involves effector Th1 cells. The destructive pattern and many of the cellular features of arteritis in IL-1ra–deficient mice resemble the human elastic-vessel arteritides, for which these mice may be a useful animal model.

Key Words: immunohistochemistry • immunology • inflammation • interleukins • receptors