Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic model

Background-Tumor necrosis factor (TNF)-alpha has been implicated in the pat hophysiology of congestive heart failure. A strain of transgenic mice (TNF1 .6) with cardiac-specific overexpression of TNF-alpha develop congestive he art failure. Methods and Results-To determine the effect of anti-TNF-alpha therapy in th is model, we studied 3 groups: TNF1.6 mice treated with saline, wild-type m ice treated with saline, and TNF1.6 mice treated with TNF-alpha neutralizin g antibody (cV1q) from 6 to 12 weeks of age. We used echocardiography to co mpare cardiac hypertrophy, function, and catecholamine response at 12 weeks of age versus baseline (6 weeks). cV1q treatment did not limit cardiac hyp ertrophy, but it significantly improved basal fractional shortening and res ponsiveness to beta -adrenergic stimulation, and it limited development of cardiac dilation. Conclusions-Blockade of TNF-alpha bioactivity by antibody therapy may both preserve cardiac function and partially reverse pathological changes in con gestive heart failure.