Analysis of cerebrospinal fluid cytokines and growth factors in multiple sclerosis patients with and without chronic headaches

Background: We previously reported that, in Japanese patients with multiple sclerosis (MS), the frequency of chronic headaches was significantly higher after administration of interferon beta (IFN beta). However, the mechanisms underlying IFN beta-related chronic headaches were unknown. Objective: To clarify the mechanisms underlying IFN beta-induced chronic headaches in MS patients by analyzing cytokine levels in cerebrospinal fluid (CSF). Methods: We measured the levels of 27 CSF cytokines and growth factors using a fluorescent bead-based immunoassay, during a headache-free period, in 34 MS patients enrolled in our previous survey on chronic headaches. Results: There were no significant differences in CSF cytokine levels between the 21 MS patients with chronic headaches and the 13 without chronic headaches. Among the 14 patients receiving IFN beta therapy, the 5 patients with chronic headaches showed significantly lower levels of interleukin (IL) 15, IL17 and chemokine (C-C motif) ligand 2 (CCL2) (also known as monocyte chemoattractant protein 1; MCP1) compared with the 9 patients without chronic headaches (P < 0.05). Conclusions: The present survey revealed that in MS, chronic headache sufferers on IFN beta therapy had decreased levels of IL15, IL17 and CCL2 in CSF. This suggests that chronic headaches may tend to develop in good responders to IFN beta.