Anti-tumor necrosis factor-alpha antibody limits heart failure in a transgenic model.
BACKGROUND
- Tumor necrosis factor (TNF)-alpha has been implicated in the pathophysiology of congestive heart failure. A strain of transgenic mice (TNF1.6) with cardiac-specific overexpression of TNF-alpha develop congestive heart failure.


RESULTS
To determine the effect of anti-TNF-alpha therapy in this model, we studied 3 groups: TNF1.6 mice treated with saline, wild-type mice treated with saline, and TNF1.6 mice treated with TNF-alpha neutralizing antibody (cV1q) from 6 to 12 weeks of age. We used echocardiography to compare cardiac hypertrophy, function, and catecholamine response at 12 weeks of age versus baseline (6 weeks). cV1q treatment did not limit cardiac hypertrophy, but it significantly improved basal fractional shortening and responsiveness 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 congestive heart failure.
Kadokami
T
T
Cardiovascular Institute of the University of Pittsburgh Medical Center Health System, Pittsburgh, PA, USA.
Frye
C
C
Lemster
B
B
Wagner
C L
CL
Feldman
A M
AM
McTiernan
C F
CF
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D005838:Genotype; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D006352:Heart Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007375:Interleukin-1 / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D051381:Rats; D012737:Sex Factors; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000318:Adrenergic beta-Agonists; D000911:Antibodies, Monoclonal; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D007545:Isoproterenol