Chemokines

Chemokines are potent proinflammatory and immune modulators. Chemokines regulate several biological processes such as chemotaxis, activation and migration of leukocytes to areas ofinflammation, collagen turnover, angiogenesis, and apoptosis (4). TNF-a and other proinflammatory cytokines, such as IL-1P and IL-6 or IFN-y, are known to induce these chemotactic polypeptides (96,97). Potent chemokines such as macrophage chemo-attractant protein-1 and macrophage inflammatory protein-1a (MIP-1a) not only can attract the monocytes and the lymphocytes, but also can modulate other functions of these cells, such as the generation of reactive oxygen species (4). Monocyte chemoat-tractant protein-1 (MCP-1) has been reported to be upregulated in experimental models of heart failure with pressure (65) or volume overload (98). Furthermore, transgenic overexpression of macrophage chemoattractant protein-1 in the myocardium has been shown to result in myocarditis and subsequent development of heart failure in experimental models (99). Similar to the proinflammatory cytokines, the failing human heart expresses chemokine and chemokine receptors (100). Increased expression of chemokines, such as MCP-1, also occurs in patients with heart failure (4). Aukrust et al. (4) reported that patients with heart failure had significantly elevated levels of all chemokines, with the highest levels in those with NYHA class IV symptoms. In their study, MCP-1 and MIP-1 a levels correlated inversely with LV ejection fraction (LVEF). Further studies on cells isolated from peripheral blood of these patients suggest that platelets; CD3+ lymphocytes; and, in particular, monocytes may contribute to the elevated C-C chemokine levels in heart failure (4).

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