Distinct inflammatory profiles across migraine states: a systematic review and meta-analysis
Emily Stuchfield-Denby, Bruno Pereira, Damien Bouvier, Radhouane Dallel, Xavier Moisset
Abstract
BACKGROUND: Although several meta-analyses have emphasised the role of inflammation in migraine, none has accounted for the diversity of its clinical manifestations. This systematic review and meta-analysis aims to provide a comprehensive and reliable assessment of cytokine levels in migraine. METHODS: We systematically searched PubMed, Embase and Cochrane up to July 4-5, 2024. Original studies providing data on cytokine levels in migraine were included. Non-inclusion criteria covered studies on hemiplegic migraine, controls with tension-type headache, and unclear cytokine identification. The meta-analysis did not cover studies involving less than 10 participants per group or lacking accessible numeral data. Summary data were extracted from each study and pooled using a random-effects model. Standardized mean differences (SMD) were calculated to compare cytokine levels across all relevant biological samples and comparison groups. FINDINGS: Fifty-seven studies were included in the narrative review and/or meta-analysis, covering 2850 migraine patients and 2814 controls. In episodic migraine patients versus controls, blood levels of interleukin-6 (SMD 0·36 [95% CI, 0.07; 0·64], P = 0·013, I²=74·0%), transforming growth factor β (SMD 0·68 [95% CI, 0·44; 0·93], P < 0·001, I²=0·0%) and C-X-C motif ligand 8 (narrative review) were elevated. Levels of interleukin-6 (narrative review; SMD 1·40 [95% CI, 0·95; 1·86], P < 0.001, I²=0·0%) and adiponectin (SMD 0·59 [95% CI, 0·19; 0·98], P = 0·003, I²=36·0%) were elevated in chronic versus episodic migraine. Levels of interleukin-1β (SMD 0·53 [95% CI, 0·15; 0·91], P = 0·006, I²=0·0%), interleukin-10 (narrative review) and salivary levels of interleukin-6 (narrative review) were elevated in ictal versus interictal migraine. No differences were found in peripheral blood cytokine levels between migraine with aura and migraine without aura. CONCLUSIONS: This study highlights the association of distinct cytokine profiles with migraine disease (interleukin-6, transforming growth factor-β, C-X-C motif ligand 8), migraine attacks (interleukin-1β, interleukin-6, interleukin-10) and migraine chronification (interleukin-6, adiponectin). Differences in inflammatory profiles across migraine clinical states have significant implications for understanding disease mechanisms, progression, and potential therapeutic interventions.