Involvement of the IL-1 system in experimental autoimmune encephalomyelitis and multiple sclerosis: Breaking the vicious cycle between IL-1β and GM-CSF

- IL-1β and IL-1R1 are both essential to the development of EAE in mice.
- Monocyte and neutrophil migration across the inflamed CNS vasculature triggers IL-1β synthesis.
- Activation of IL-1R1 signaling in CNS-ECs and TH cells stimulates GM-CSF production.
- IL-1β and GM-CSF are interacting to create a vicious cycle of neuroinflammation.
- Inhibition of IL-1β/IL-1R1 signaling is a promising target for the treatment of MS.

Multiple sclerosis (MS) is an autoimmune disease that affects hundreds of thousands of people worldwide. Given the autoimmune nature of the disease, a large part of the research has focused on autoreactive T and B cells. However, research on the involvement of myeloid cells in the pathophysiology of MS has received a strong and renewed attention over the recent years. Despite the multitude of inflammatory mediators involved in innate immunity, only a select group of cytokines are absolutely critical to the development of CNS autoimmunity, among which is interleukin (IL)-1. While the importance of the IL-1 system in experimental autoimmune encephalomyelitis (EAE) and MS has been recognized for about 20 years, it is only recently that we have begun to understand that IL-1 plays multifaceted roles in disease initiation, development, amplification and chronicity. Here, we review the recent findings showing an implication of the IL-1 system in EAE and MS, and introduce a model that highlights how IL-1β and granulocyte-macrophage colony-stimulating factor (GM-CSF) are interacting together to create a vicious feedback cycle of CNS inflammation that ultimately leads to myelin and neuronal damage.