Distinct Alterations of Inflammatory Biomarkers in Cluster Headache: A Case Control Study

Investigate the immune system's role in cluster headache by analyzing cytokines in people with cluster headache and headache-free controls, and explore if certain cytokines could predict a specific phenotype.

We measured 45 cytokines in adult participants from the Danish Cluster Headache Biobank in a prospective case-control setup. People with cluster headache were diagnosed according to the International Classification of Headache Disorders third-edition. Controls were matched for age and sex.

A total of 412 were analyzed deriving from 99 with chronic cluster headache, 108 with episodic cluster headache (ECH) in bout, 105 with ECH in remission, and 100 successfully matched controls. Compared with controls, 13 cytokines were altered for ECH in bout (p < 0.05), 3 in remission (p < 0.05), and 10 for chronic cluster headache (p < 0.05). Oncostatin m was significantly elevated in all 3 disease states compared with controls (p < 0.05). Overall, the investigated cytokines showed distinct patterns of alterations between chronic cluster headache and episodic cluster headache in bout and, interestingly, IL-1β was significantly associated with having chronic cluster headache rather than episodic in bout in a logistic regression model adjusting for potential confounders (p < 0.05).

Findings show that the immune system is altered in all 3 states of cluster headache compared with controls. Oncostatin m was elevated, constituting a promising target for future studies. The distinct alterations between episodic and chronic cluster headache are striking and urges further research of the immune system in cluster headache to better understand its potential role in prediction of disease activity and treatment response. ANN NEUROL 2025;98:4-18.