IL-1 receptor antagonist-deficient (IL-1Ra−/−) mice spontaneously develop AS, and T-cells from IL-1Ra−/− produce much higher levels of TNF-α after anti-CD3 antibody stimulation compared to wild-type mice; furthermore, TNF-α deficiency completely suppressed AS development in IL-1Ra−/− mice, suggesting that TNF-α actively participates in AS development in IL-1Ra−/− mice [52]. Here, TNF is linked to aortic stenosis.