GM-CSF is a marker of compartmentalised intrathecal inflammation in multiple sclerosis

Abstract

Background: Granulocyte-macrophage colony stimulating factor (GM-CSF) is a pro-inflammatory cytokine secreted by various immune cells. Several studies have demonstrated an expansion of GM-CSF producing T cells in the blood or CSF of people with MS (pwMS). However, whether this equates to greater concentrations of circulating cytokine remains unknown as quantification is difficult with traditional assays. Objective: To determine whether GM-CSF can be quantified and whether GM-CSF levels are elevated in pwMS. Methods: We employed Single Molecule Array (Simoa) to measure GM-CSF in both CSF and blood. We then investigated relationships between GM-CSF levels and measures of blood–CSF-barrier integrity. Results: GM-CSF was quantifiable in all samples and was significantly higher in the CSF of pwMS compared with controls. No association was found between CSF GM-CSF levels and Q-Albumin – a measure of blood–CSF-barrier integrity. CSF GM-CSF correlated with measures of intrathecal inflammation, and these relationships were greater in primary progressive MS compared with relapsing-remitting MS. Conclusion: GM-CSF levels are elevated specifically in the CSF of pwMS. Our results suggest that elevated cytokine levels may reflect (at least partial) intrathecal production, as opposed to simple diffusion across a dysfunctional blood–CSF-barrier.