Could galcanezumab modulate inflammatory cytokines? A single-centre exploratory study

Journal article

Introduction: Migraine is a highly disabling neurological disorder. The pathophysiological mechanisms underlying this condition are complex and not yet fully elucidated. While calcitonin gene-related peptide (CGRP) plays a pivotal role in the genesis of migraine, not all patients respond to CGRP-targeted therapeutic interventions, suggesting the involvement of alternative mechanisms such as neuroinflammation. In this context, cytokines may act as modulators of inflammatory responses associated with migraine. The objective of this study is to evaluate cytokine profiles in patients with episodic and chronic migraine in comparison with healthy controls and to investigate the modulatory effect of galcanezumab treating episodic migraine patients. Methods: in this prospective pilot study, 17 patients with high-frequency episodic migraine (EM), 18 with chronic migraine (CM), and 17 healthy controls (HC) were enrolled. Plasma cytokine levels (IFN-γ, IL-1β, IL-10, IL-6, TNF-α) were measured using multiplex immunoassay during the interictal phase. Blood samples of the EM group eligible for treatment with galcanezumab were additionally collected at three time points: baseline (T0) and 5 and 27 days after administration of galcanezumab (T5, corresponding to the maximum serum concentration (Cmax), and T27, drug half-life, respectively). Results: In comparison with patients diagnosed with CM and HC, EM patients demonstrated elevated interictal levels of IFN-γ, IL-1β, IL-6 and IL-10 (p < 0.001). In perspective analyses, a significant decrease in cytokine levels was observed in the galcanezumab-treated group at Cmax (T5) for IFN-γ, IL-1β, IL-10, and TNF-α, but not for IL-6 (p = 0.640). Discussion: This study highlights distinct cytokine profiles associated with chronic and episodic migraine. Treatment with galcanezumab was associated with a transient reduction in both pro- and anti-inflammatory cytokines during the first month of therapy. These findings support the hypothesis that CGRP could influence the inflammatory pathways in migraine pathophysiology.

Authors: Ceccardi, G; Rao, R; Schiano di Cola, F; Fiducia, B; Tolassi, C

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Springer
• Journal: Journal of Neurology
• Volume: 273
• Issue: 2
• Publication date: 2026-02-01
• DOI: 10.1007/s00415-026-13706-3
• EISSN: 1432-1459
• ISSN: 0340-5354
• Language: English
• Keywords: Tumor necrosis factor alpha; Calcitonin gene-related peptide; Cytokine; Chronic Migraine; Migraine; Inflammation; Microglia; Neurology