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(Circulation. 1999;100:e84.)
© 1999 American Heart Association, Inc.

Circulation Electronic Pages

Tumor Necrosis Factor- and Interleukin-10 Genotypes in Congestive Heart Failure

Nicholas Jenkins, MB, ChB, MRCP(UK)

Wythenshawe Hospital Manchester, UK

	Introduction

 
To the Editor:

The allelic case-control study by Kubota et al¹ suggests that polymorphisms at positions -308 and +252 of the tumor necrosis factor- (TNF-) gene do not influence either risk of heart failure or plasma levels of TNF- for patients with heart failure. The investigators recognize the potential biases of patient selection inherent in the study and suggest that patients homozygous for TNFA2 or TNFB2 could have had a more "malignant" clinical course such that mortality was high before presentation at a participating center. However, the isolated assessment of TNF- genotypes and plasma levels may be misleading without consideration of other interacting cytokines.

Although TNFA2 and TNFB2 have been correlated with increased TNF- release by endotoxin-stimulated leukocytes, in vivo control of TNF- synthesis is complex and downregulated by anti-inflammatory cytokines including interleukin (IL)-4 and IL-10. An autoregulatory loop appears to exist whereby TNF- induces IL-10 production, which ultimately reduces TNF- synthesis.² Three functional polymorphisms have been described for the IL-10 promoter, with single base pair substitutions at positions -1082, -819, and -592.³ In particular, substitution of guanine for adenine at position -1082 has been correlated with low IL-10 production after T-cell stimulation.³ The potential clinical importance of this finding was highlighted by a recent study⁴ demonstrating a strong association between the combined low IL-10/high TNF- (TNFA2) genotype and early graft rejection in a population of heart transplant recipients. Other recent studies⁵ have demonstrated the complementary importance of IL-10 and TNF- in patients with bacterial sepsis and have indicated . . . [Full Text of this Article]