Macrophage inflammatory protein-1 alpha relates to the recruitment of inflammatory cells in myosin-induced autoimmune myocarditis in rats

In experimental autoimmune myocarditis (EAM) there is a characteristic init ial focal inflammatory response in the myocardium, induced mainly by CD4(+) T cells and macrophages, which leads to massive myocardial damage. Macroph age inflammatory protein-1 alpha (MIP-1 alpha) induces chemotaxis in lympho cytes, eosinophils, basophils, and macrophages. We assessed the potential r ole of MIP-I a in the pathogenesis of EAM in rats immunized with porcine my osin. Following immunization, the levels of MIP-1 alpha mRNA in EAM showed an increase on Day 11 and peaked on Day 17. MIP-1 alpha -positive cells wer e predominantly immunoreactive to OX6 antibody (dendritic cells) and ED2 an tibody (resident macrophages) by Day 14. Marked cellular infiltration was s een on Day 17 with the major population of MIP-1 alpha -positive cells also positive for ED1 (inflammatory macrophages). We then examined the associat ion of MIP-1 alpha with the development of myocardial inflammation. Rats we re divided into three groups: Group A consisted of EAM rats (n = 10); Group B consisted of EAM rats treated with anti-MIP-1 alpha (1 mg/kg) on Days 11 , 13, and 15, before the onset of initial inflammation (n = 5): and Group C consisted of EAM rats treated with anti-MIP-la from the start of the initi al inflammation on Days 14, 16, and 18 (n = 5). Rats were euthanized on Day 21 and three transverse sections of the heart were prepared to determine t he percentage of the area affected by inflammatory lesions. This area of in flammation was significantly smaller in Group B (27 +/- 4%) than in Groups A (51 +/- 6%) or C (50 +/- 6%)(p < 0.01), indicating that the administratio n of antibody before the initiation of inflammation, in part, will inhibit myocardial inflammation. These data suggest that MIP-1 alpha may play an im portant role in the recruitment of inflammatory cells in the early stages o f EAM.