GM-CSF Cytokine Production Contributes to Multiple Sclerosis Development

In a recent study entitled “Expression of GM-CSF in T Cells Is Increased in Multiple Sclerosis and Suppressed by IFN-β Therapy,” researchers unraveled a key role for the cytokine GM-CSF in multiple sclerosis progression, suggesting GM-CSF as a target of IFN-β therapy. The study was published in The Journal of Immunology.

Multiple sclerosis (MS) is a chronic autoimmune disease characterized by a patient’s own immune system attacking the central nervous system, specifically myelin, a component that insulates nerve fibers and maintains a current of neuronal signals. Immune cells release chemical signals called cytokines that act as messengers and chemoattractants for other immune cells, driving inflammation in the brain and contributing to disease progression, marked by neuron death. However, while cytokines are a known established factor in the pathogenesis of MS, which cytokines are the driver of MS has remained a matter of debate.

In this study, a team of researchers followed their previous results suggesting that a specific subset of T cells, Th-17 cells, produced a cytokine – GM-CSF (short for Granulocyte Macrophage Colony-Stimulating Factor) — that was key in triggering brain inflammation. Moreover, in mouse models of MS disease, the team discovered that those unable to produce GM-CSF never developed the disease. As such, researchers determined if the same effect was observed in human patients with MS and how IFN-therapy, a commonly used treatment, impacted GM-CSF production.

The team assessed GM-CSF expression in blood samples of MS patients treated with IFN-β and in those left untreated. Additionally, they also determined GM-CSF production in brain lesions of deceased MS patients and compared those with MS-untreated patients and healthy individuals. They found that untreated patients had significantly higher numbers of GM-CSF producing T cells when compared to IFN-β–treated MS patients or healthy individuals. The same was observed in brain samples, with increased numbers of GM-CSF-producing cells in MS patients.

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According to the authors, these findings show increased GM-CSF production contributes to MS pathogenesis and suggests that IFN-β therapy may benefit MS patients by inhibiting GM-CSF expression. Importantly, the preliminary result of a recent Phase 1 clinical trial showed that antibody-blocking GM-CSF may benefit MS patients.

Study lead author Abdolmohamad Rostami, M.D., Ph.D., Chair of the Department of Neurology at Thomas Jefferson University commented, “After our animal studies showed that GM-CSF was important in the development of an MS-like disease, we were excited to see these results confirmed using samples from MS patients in the current study. We hope that this research showing GM-CSF is an important target will lead us toward therapies that more effectively block the damaging immune reaction in the central nervous system of MS patients.”