Interleukin 6 (IL-6) is a typical pleiotropic cytokine that modulates a variety of physiological events in vertebrates, including cell proliferation, differentiation, survival, and apoptosis, among other functions. IL-6 plays roles in the immune, the endocrine, the nervous, and the hematopoietic systems, in bone metabolism, regulation of blood pressure and inflammation. IL-6 exerts its effects on different tissues and organ systems. Many cell types are reported to produce IL-6: T cells, B cells, polymorphonuclear cells, eosinophils, monocyte/macrophages, mast cells, dendritic cells, chondrocytes, osteoblasts, endothelial cells, skeletal and smooth muscle cells, islet cells, thyroid cells, fibroblasts, mesangial cells, keratinocytes, microglial cells, astrocytes, oligodendrocytes, adipose tissue and certain tumor cells. Here, we review the participation of the IL-6 in the neuroimmunoendocrine network. The specific targeting of the IL-6 pathway can be a promising new approach for the treatment and prevention of neurodegenerative disorders in humans as well as improving the autoinflammatory process both systemically and locally.