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Granulocyte-macrophage colony-stimulating factor: Increased expression by immune cells of patients with multiple sclerosis

      Background: Recent evidence suggests that GM-CSF Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF), a proinflammatory cytokine with multiple roles in the immune system, has a role in MS pathogenesis. In the experimental model of MS, experimental autoimmune encephalomyelitis, expression of GMCSF by T cells is essential for disease induction. Our aim was to evaluate the expression of GM-CSF by different peripheral blood mononuclear cells (PBMC) subtypes in MS patients and controls.
      Materials and methods: PBMCs were isolated 21 MS and 14 control subjects and stimulated. NK cells were isolated and cultured with different stimuli for 3 days. Cells were phenotyped using flow cytometry.
      Results: There was higher GM-CSF expression in Phorbol Myristate Acetate/Ionomycin (PMA/I)-stimulated monocyte-gated PBMCs, and natural killer T (NKT) cells in MS patients compared to healthy controls. Th17, NK, and cytotoxic T-gated cells expressed similar GM-CSF levels in MS and controls In MS, 40–45% of gated CD4+ and CD8 cells expressing GM-CSF; 10–20% of these are also IFN-γ+. About 50% of NKT cells are GMCSF+, and 45% of these were IFN-γ+. In controls, these proportions were lower. Isolated NK cells stimulated with IL-15+IL-18, and IL-15+IL-1β were noticed to have more GM-CSF expression than the unstimulated and mono-stimulated CD56+ NK cells (MS n = 6, controls n = 6).
      Conclusion: T cells (both CD4+ and CD8+), NK, and NKT cells are all high GM-CSF producers in MS. GM-CSF is a potential therapeutic target in MS. The recent safety and tolerability results of a phase I trial of a monoclonal antibody in MS are encouraging.