ELEVATED CIRCULATING LEVELS OF C-C CHEMOKINES IN PATIENTS WITH CONGESTIVE-HEART-FAILURE

Background - Immunologic and inflammatory responses appear to play a p athogenic role in the development of congestive heart failure (CHF). A ctivation and migration of leukocytes to areas of inflammation are imp ortant factors in these immunologic responses. Because the C-C chemoki nes are potent chemoattractants of monocytes and lymphocytes and can m odulate other functions of these cells (e.g. generation of reactive ox ygen species), we measured circulating levels of three C-C chemokines in CHF. Methods and Results - Levels of macrophage chemoattractant pro tein-1 (MCP-1), macrophage inflammatory protein-let (MIP-1 alpha), and RANTES (regulated on activation normally T-cell expressed and secrete d) were measured by enzyme immunoassays in 44 patients with CHF and 21 healthy control subjects. CHF patients had significantly elevated lev els of all chemokines with the highest levels in New York Heart Associ ation class IV, and MCP-1 and MIP-1 alpha levels were significantly in versely correlated with left ventricular ejection fraction, Elevated C -C chemokine levels were found independent of the cause of the heart f ailure, but MCP-1 levels were particularly raised in patients with cor onary artery disease, Studies on cells isolated from peripheral blood suggested that platelets, CD3+ lymphocytes, and in particular, monocyt es, 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 o n O-2(-) generation in monocytes, which was inhibited by neutralizing antibodies against MCP-1. Conclusions - This first demonstration of in creased circulating levels of C-C chemokines in CHF with particularly high levels in patients with severe disease may represent previously u nrecognized pathogenic factors in CHF.