Colony-stimulating factors and coxsackievirus B3 myocarditis in mice: Macrophage colony-stimulating factor suppresses acute myocarditis with increasing interferon-α

Abstract

The effects of macrophage colony-stimulating factor (M-CSF) and granulocyte colony-stimulating factor (G-CSF) on murine coxsackievirus B3 myocarditis were investigated. A total of 4 × 106 U/kg/day M-CSF and 20 μg/kg/day G-CSF were injected subcutaneously every day on day 0 to day 14 starting simultaneously with virus inoculation. Serum interferon-α was measured periodically. The survival rate of the M-CSF group was higher than that of the untreated control group (p < 0.05). On days 7 and 14 cardiac disease was significantly lower in the M-CSF group than in the untreated control group. Myocardial virus titers on day 7 in the M-CSF group were lower compared with those of the untreated control group. No significant difference was seen in the survival, cardiac disease, or myocardial virus titers between the G-CSF and the control groups. Monocyte counts on days 7 and 14 in the M-CSF group were increased compared with those in the control group. Serum interferon-α titers in the M-CSF and G-CSF groups on day 4 and those in the M-CSF group on day 7 were significantly increased in comparison with those of the untreated control group. We conclude that M-CSF but not G-CSF has the potency to limit myocardial virus titers and to reduce cardiac disease in the acute coxsackievirus B3 myocarditis. This ability is associated with an elevated interferon-α. Thus macrophages may play a defensive role in this model.