Interaction between chemokines and oxidative stress: Possible pathogenic role in acute coronary syndromes

OBJECTIVES We sought to study the relationships between chemokines and oxid ative stress in acute coronary syndrome. BACKGROUND In view of existing knowledge on the participation of leukocytes and oxidative stress in the pathogenesis of acute coronary syndrome, we hy pothesized that chemokines may play a role in recruiting and activating leu kocytes in this disorder. METHODS The levels of chemokines and oxidative stress were studied in 38 pa tients with stable and 38 with unstable angina and in 20 controls. In separ ate in vitro experiments the effect of chemokines on reactive oxygen specie s in monocytes and the effect of antioxidants on chemokine levels in these cells were also studied. RESULTS 1) Angina patients had raised serum levels of chemokines in both cr oss-sectional and longitudinal testing, with particularly high levels of in terleukin (IL)-8, monocyte chemoattractant protein (MCP)-1 and macrophage i nflammatory peptide (MIP)-1-alpha in unstable disease. 2) T cells, and part icularly monocytes, seem to contribute to the raised IL-8, MCP-1 and MIP-l- alpha levels in unstable angina. 3) Concomitantly, and significantly correl ated with MCP-1 and IL-8 levels, stable and particularly unstable angina pa tients had decreased plasma levels of antioxidants and increased lipid pero xidation, suggesting enhanced oxidative stress. 4) Monocyte chemoattractant protein-1 enhanced the generation of O-2(-) In monocytes from unstable ang ina patients, and the antioxidant glutathione-monoethyl ester suppressed th e production of IL-8 and MCP-1 in these cells. CONCLUSIONS Our findings suggest an interaction between chemokines and oxid ative stress in unstable angina. This interaction may represent a vicious c ircle involved in the pathogenesis of acute coronary syndromes. (C) 2001 by the American College of Cardiology.