Immunex' TNFR:Fc Offers New Approach To CHF

18 November 1997

Immunex' soluble tumor necrosis factor receptor Enbrel is alreadyshowing promise in the treatment of rheumatoid arthritis and Crohn's disease, and a Phase I study presented at the 70th Scientific Sessions of the American Heart Association now suggests a new indiction - congestive heart failure.

Douglas Mann of Baylor College of Medicine in Houston, Texas, in his presentation of the data, noted that this is the first time that a pharmacologic therapy has been used to modulate this system in CHF. TNF-alfa levels are known to become persistently elevated in patients with CHF, with dramatic consequences.

Dr Mann believes that the TNF system has evolved as a proinflammatory defence mechanism against major trauma, but in the case of the heart it is overexpressed after ischemia and reperfusion. TNF-alfa stimulates cardiac myocytes to express adhesion molecules (notably ICAM-1), which promotes infiltration of the tissue with macrophages and neutrophils. Release of other cytokines, leukotrienes and free radicals from these leukocytes results in myocyte death and destruction of the matrix, cardiac remodelling, and a decrease in left ventricular ejection fraction. This can then lead to cardiomyopathy and pulmonary edema. TNF-alfa also acts as a negative inotrope, further compromising the function of the failing heart.

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