IL-1Ra-deficient mice showed increased aortic valve leaflet thickness compared to wild-type mice at 12 weeks of age (P<0.001), a process mediated by T-cell derived TNF-alpha.
IL-1Ra deficiency induces aortic valve inflammation and stenosis in mice, a process that is importantly mediated by TNF-alpha.
p-value: p=<0.001
OBJECTIVE: Interleukin-1 receptor antagonist (IL-1Ra), one of the most important antiinflammatory cytokines, is crucial for homeostasis of the immune system. However, the role of IL-1Ra in aortic valve stenosis (AS) remains poorly understood corrected. METHODS AND RESULTS: IL-1Ra-deficient (IL-1Ra(-/-)) mice on the BALB/c background showed increased aortic valve leaflet thickness compared to wild-type mice at the age of 12 weeks (P<0.001). We used peripheral T-cell transplantation to examine the role of T cells in the development of AS. T cells from IL-1Ra(-/-) but not from wild-type mice induced increased aortic valve thickness in nu/nu mice. Moreover, IL-1Ra(-/-) T cells produced much higher levels of tumor necrosis factor (TNF)-alpha in culture supernatants after anti-CD3 antibody stimulation compared to wild-type mice (P<0.001). Finally, we studied the role of TNF-alpha in the development of AS in IL-1Ra(-/-) mice by generating double-gene-deficient (TNF-alpha(-/-)/IL-1Ra(-/-)) mice. Interestingly, TNF-alpha(-/-)/IL-1Ra(-/-) mice did not have AS. CONCLUSIONS: IL-1Ra deficiency in inflammatory cells induced aortic valve inflammation and TNF-alpha participates importantly in the development of AS in IL-1Ra(-/-) mice.
Isoda et al. (2010) studied Aortic valve stenosis. IL-1Ra deficiency vs. Wild-type mice was evaluated on Aortic valve leaflet thickness (p=<0.001). IL-1Ra-deficient mice showed increased aortic valve leaflet thickness compared to wild-type mice at 12 weeks of age (P<0.001), a process mediated by T-cell derived TNF-alpha.