Objective-Inflammation plays an important role in atherosclerosis. One of the most potent pro-inflammatory cytokines is tumor necrosis factor-␣ (TNF-␣), a cytokine identified to have a pathogenic role in chronic inflammatory diseases such as rheumatoid arthritis (RA). The aim of the study was to evaluate the importance of TNF-␣ in atherogenesis. Methods and Results-Mice deficient in both apolipoprotein E (apoE) and TNF-␣ were compared regarding their atherosclerotic burden. Mice were fed a Western-style diet (WD) or normal chow. Mice deficient in both apoE and TNF-␣ exhibited a 50% (Pϭ0.035) reduction of relative lesion size after 10 weeks of WD. Bone marrow transplantation of apoE o mice with apoE o tnf-␣ o bone marrow resulted in a 83% (Pϭ0.021) reduction after 25 weeks on WD. In apoE knockout mice treated with recombinant soluble TNF receptor I releasing pellets, there was a reduction in relative lesion size after 25 weeks of 75% (Pϭ0.018).Conclusions-These findings demonstrate that TNF-␣ is actively involved in the progression of atherosclerosis.Accordingly, TNF-␣ represents a possible target for prevention of atherosclerosis. This may be of particular importance in rheumatoid arthritis because these patients have an increased risk for cardiovascular disease.

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