Burchfield JS et al. (2008) Interleukin-10 from transplanted bone marrow mononuclear cells contributes to cardiac protection after myocardial infarction. Circ Res 103: 203–211

Stumpf C et al. (2008) Interleukin-10 improves left ventricular function in rats with heart failure subsequent to myocardial infarction. Eur J Heart Fail 10: 733–739

Interleukin (IL)-10 exerts potent anti-inflammatory effects in vivo via inhibition of the production of various cytokines and chemokines. Serum levels of this molecule have been shown to correlate with prognosis in patients with acute coronary syndromes. IL-10 administration is, therefore, considered a potential treatment for patients after myocardial infarction (MI). Two recent rodent studies have reported beneficial effects of IL-10 therapy on inflammation and remodeling after MI.

In humans, intracoronary transplantation of bone-marrow-derived progenitor cells after acute MI results in improved left ventricular function. Bone-marrow-derived progenitor cells express high levels of IL-10 and Burchfield et al. hypothesized that IL-10 mediates much of the beneficial effect of these cells in patients after MI. Bone marrow mononuclear cells (BM-MNCs) were isolated from IL-10-deficient and wild type (control) mice to test this hypothesis.

Ligation of the left anterior descending coronary artery was performed in female mice to result in MI. This procedure and was immediately followed by intramuscular injection of diluent with and without BM-MNCs from wild type or IL-10-deficient mice into the infarcted area. IL-10 was required for the protective effects of BM-MNCs on left ventricular function; this protection possibly resulted from IL-10 suppression of T-cell infiltration, but not from limitation of neutrophil infiltration. IL-10 was not required for BM-MNC-stimulated neovascularization or for BM-MNC secretion of the proangiogenic cytokines IL-6, monocyte chemotactic protein 1, vascular endothelial growth factor and insulin-like growth factor 1.

Stumpf and colleagues' approach to studying the effects of IL-10 therapy on inflammation and remodeling after MI was to treat rats with a subcutaneous injection of recombinant human (rh) IL-10 immediately after induction of MI (via ligation of the left anterior descending coronary artery) and then to inject rhIL-10 subcutaneously every day for the next 4 weeks. Animals were assessed at the 4-week time point.

In agreement with the results from Burchfield and colleagues' study of BM-MNC-secreted IL-10, administration of rhIL-10 protected rats from MI-induced left ventricular dysfunction. In rats that underwent ligation of the left anterior descending coronary artery but received no IL-10, membrane-bound and circulatory concentrations of tumor necrosis factor and IL-6, as well as serum levels of monocyte chemotactic protein 1, were substantially increased after MI. Interestingly, membrane-bound and soluble IL-10 levels were decreased. Subcutaneous administration of rhIL-10 attenuated the increases in tumor necrosis factor, IL-6 and monocyte chemotactic protein 1 that were associated with MI. In line with these findings, IL-10 suppressed macrophage infiltration after MI.

IL-10, therefore, exerts protective effects on left ventricular function when administered after MI, possibly by suppression of T-cell and macrophage infiltration. These studies suggest that IL-10 could be a good therapeutic option for patients who have undergone MI.