Skeletal muscle secrets several bioactive molecules known as myokines. Interleukin-6 (IL-6) has been described as a myokine secreted in response to skeletal muscle injury as well as to macrophage invasion in inflammation. To our knowledge no connection between macrophages and skeletal muscle regarding IL-6 secretion has been described so far. Here we report that co-culturing of C2C12 cells with RAW macrophages enhances IL-6 secretion of the cells cultured together. However, this is not seen in cross-feeding experiments, where culture medium of RAW macrophage culture is used as the culture medium of C2C12 cells or vice versa. Pravastatin, known to induce myopathy, also stimulates IL-6 production in monocultured C2C12 cells and elevates IL-6 concentration in the culture medium of the co-cultures. These results indicate an intricate interaction between skeletal muscle and macrophages in inflammation related to IL-6 production.