Cytokine levels in cluster headache patients

Objective: The pathophysiology of cluster headache while much debated, is still largely unknown. Most studies have focused on vascular or neural mechanisms. ¹Exciting new research is directed at examining possible neuroimmunologic mechanisms.² The objective of the study was to test and expand a hypothesis that cluster headache has a neuroimmunologic mechanism. Urinary pro-inflammatory cytokine levels of IL-1B, TNFα, and IL-6 in cluster patients during and outside of headache cycle versus nonheadache controls were studied to determine whether differences exist and how this may contribute to our understanding of cluster pathogenesis. Future objectives were to find a diagnostic marker for cluster headache among cytokine samples, to gauge therapeutic response to treatment by cytokine measurements, and to contribute to therapeutic applications for immune modulation. Methods: Urinary levels of pro-inflammatory cytokines interleukin 1 beta (IL-1B), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNFα) were studied in 11 male episodic cluster headache patients during and outside of active headache cycles and compared with healthy nonheadache male control subjects. Results: Comparative means revealed lower levels of all cytokines tested in cluster subjects versus controls, but did not achieve statistical significance. No differences were found between duster headache groups during and outside of headache cycles. Conclusions: Lower levels of interleukin IL-1B, IL-6, and TNFα in cluster headache patients may signify a disordered bidirectional neuroimmune network that may cause, contribute to, occur independent of, or be an associated epiphenomenon of cluster headache pathophysiology. Further research to expand proposed neuroimmunologic mechanisms of cluster headache may contribute to diagnostic markers of disease or future therapeutic modalities such as recombinant cytokines, cytokine antagonists, or medications to modulate cytokine production.