Elevated circulating levels of C-C chemokines in patients with congestive heart failure.

Abstract

Immunologic and inflammatory responses appear to play a pathogenic role in the development of congestive heart failure (CHF). Activation and migration of leukocytes to areas of inflammation are important factors in these immunologic responses. Because the C-C chemokines are potent chemoattractants of monocytes and lymphocytes and can modulate other functions of these cells (eg, generation of reactive oxygen species), we measured circulating levels of three C-C chemokines in CHF. Levels of macrophage chemoattractant protein-1 (MCP-1), macrophage inflammatory protein- 1alpha (MIP-1alpha), and RANTES (regulated on activation normally T-cell expressed and secreted) were measured by enzyme immunoassays in 44 patients with CHF and 21 healthy control subjects. CHF patients had significantly elevated levels of all chemokines with the highest levels in New York Heart Association class IV, and MCP-1 and MIP-1alpha levels were significantly inversely correlated with left ventricular ejection fraction. Elevated C-C chemokine levels were found independent of the cause of the heart failure, but MCP-1 levels were particularly raised in patients with coronary artery disease. Studies on cells isolated from peripheral blood suggested that platelets, CD3+ lymphocytes, and in particular, monocytes, might contribute to the elevated C-C chemokine levels in CHF. The increased MCP-1 levels in CHF were correlated with increased monocyte activity reflected in an enhancing effect of serum from CHF patients on O2-generation in monocytes, which was inhibited by neutralizing antibodies against MCP-1. This first demonstration of increased circulating levels of C-C chemokines in CHF with particularly high levels in patients with severe disease may represent previously unrecognized pathogenic factors in CHF.