Reduced expression of inflammasome complex components in cluster headache

Abstract

Background:The involvement of inflammation in the pathophysiology of cluster headache (CH) has been suggested, with a role implied for interleukin (IL)-1β. We aimed to measure peripheral blood expression levels of IL-1β-inducing systems, the inflammasome complex, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling, and investigate their values as putative biomarkers in CH. Methods:In this cross-sectional study conducted in the Headache Unit of Istanbul University, Turkey, blood mononuclear cells (PBMCs) and sera were collected from 30 patients with episodic migraine, 4 with chronic CH, and 47 healthy individuals. Levels of inflammasome complex components (NLRP1, NLRP3, caspase 1, and ASC), end products of inflammasome complex activity (IL-1β, IL-18, and nitric oxide synthase isoforms), neuron-specific enolase, other inflammatory factors (NF-κB, HMGB1, and s100b), and anti-inflammatory IL-4 were measured by real-time quantitative polymerase chain reaction and/or enzyme-linked immunosorbent assay.Results: NLRP3 expression levels were significantly reduced in PBMC samples of patients with CH, obtained during CH attacks (n = 24) or headache-free (out of cycle) episodes (n = 10). CH-attack patients showed greater expression levels of IL-1β (2 −ΔΔCT

Biomarkers in cluster headache: A systematic review

“…The remaining 40 studies met eligibility criteria and altogether summed 832 patients with CH 6–46 . In total, 781 of the patients had the diagnosis confirmed by the ICHD‐1, ‐2, ‐3b, or ‐3 criteria.…”

“…Eight studies investigated the association between CH and markers of inflammation carried out between 1992 and 2022 36–44 . Study populations ranged between 8 and 34, variably representing the three disease states eCHb, eCHr, and cCH.…”

“…On the contrary, findings for IL-2 showed a trend toward increased expression in eCH compared to HCs, measured by respectively IL-2 gene expression 41 and IL-2-receptor levels. 43 Interestingly, increased IL-2 gene expression was reported to be highest in the interictal phase and not during the ictal phase in eCHb.…”

“…Eight studies investigated the association between CH and markers of inflammation carried out between 1992 and 2022. [36][37][38][39][40][41][42][43][44] Study populations ranged between 8 and 34, variably representing the three disease states eCHb, eCHr, and cCH. The source of sample specimen was blood sera or whole blood for all studies except for one examining CSF.…”

“…Most frequently examined were interleukins, more specific interleukin 1 (IL-1), 42 2 (IL-2), 41,42 6 (IL-6), 18 (IL-18), 43 1-a (IL-1a), 37 and 1-b (IL-1b). 37,40,43 Findings for IL-1a and IL-1b were divergent, as Marteletti et al reported significantly increased levels of IL-1b in both eCHb and eChr compared to HC, 40 whereas Bussonne et al…”