Enhanced expression and production of monocyte chemoattractant protein-1 in myocarditis

Monocyte chemoattractant protein-1 (MCP-1) is a member of the C-C chemokine family that has been shown to play a major role in the migration of monocy tes and T cells to an inflammatory focus. To clarify the role of MCP-1 in t he pathogenesis of myocarditis, we have examined the expression of MCP-1 in rat hearts with experimental autoimmune myocarditis (EAM), and have also m easured serum levels of MCP-1 in patients with histology-proven acute myoca rditis. Lewis rats were immunized with cardiac myosin and were killed 9, 12 , 15, 18, 21, 24, 27, 30, 33, 36, 42 and 56 days after immunization. Large mononuclear cells in the myocardial interstitium were stained with an anti- MCP-1 antibody. mRNA of MCP-1 increased in the hearts of EAM rats from days 15-27 as shown by quantitative reverse transcription-polymerase chain reac tion. Serum MCP-1 levels of the rats with EAM were significantly elevated f rom days 15-24. In the clinical study, serum levels of MCP-1 in 24 patients with acute myocarditis at the time of admission (165.2 +/- 55.8 pg/ml) wer e significantly (P = 0.0301) elevated compared with those of 20 healthy vol unteers (61.8 +/- 10.7 pg/ml). Serum MCP-1 levels of 8 fatal cases (371.8 /- 145.2 pg/ml) were significantly (P = 0.0058) higher than those of 16 cas es who survived (65.5 +/- 12.8 pg/ml). In conclusions, MCP-1 may play an im portant role in the pathogenesis of human acute myocarditis as well as in t he progression of rat EAM.