Distinct inflammatory profiles across migraine states: a systematic review and meta-analysis

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.

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.

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.

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.