TNFα-antagonist neither improve cardiac remodelling or cardiac function at early stage of heart failure in diabetic rats

Abstract

Objectives: Despite tumor necrosis factor alpha (TNFα) has been shown to be a prognostic marker in patients with heart failure and previous preclinical study with TNFα-antagonist has been demonstrated to improve cardiac function in acute heart failure, recent clinical trials using TNFα-antagonist in patients with chronic severe heart failure have been disappointing. The aim was to study why TNFα-antagonist may not work during long-term treatment in chronic heart failure (CHF) in experimental model.

Methods: 49 rats were used at the age of 26 weeks: healthy Whistar Kyoto rats (WKY, n = 26) and diabetic (WKY+D, n = 23). Rats in each group received either a 12-week treatment with TNFα-antagonist (Etanercept) or NaCl injections.

Results: In diabetic rats, there were increased plasma glucose level and blood pressure. By use of echocardiography diabetic rats displayed not only enlarged and thinned left ventricles but also decreased both systolic and diastolic functions. Moreover, there are increased interleukin-6 (IL6) mRNA levels. However, TNFα-antagonist, etanercept, does not improve either cardiac remodelling or cardiac function. IL6 mRNA level remained unchanged after treatment of etanercept.

Conclusion: Chronic treatment of TNFα-antagonist has no favourable effect on either cardiac remodelling or cardiac function. It is therefore inappropriate to use TNFα-antagonist in CHF in diabetes as underlying cause.

• TNFα-antagonist
• cardiac remodelling
• cardiac function
• diabetes

Acknowledgements

This study was supported by grants from Swedish Medical Research Council, Swedish Heart–Lung Foundation and Sahlgrenska University Hospital.

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.