Reduced expression of inflammasome complex components in cluster headache.

Abstract

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. 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. 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 median [25th-75th percentile], 0.96 [0.66-1.29 vs. 0.52 [0.43-0.73]) and NF-κB (1.06 [0.66-3.00] vs. 0.62 [0.43-1.19]) in PBMCs but not in sera compared with headache-free CH patients. However, these differences did not attain statistical significance (p=0.058 and p=0.072, respectively). Moreover, NLRP1 (52.52 [35.48-67.91] vs. 78.66 [54.92-213.25]; p=0.017), HMGB1 (11.51 [5.20-15.50] vs. 13.33 [8.08-18.13]; p=0.038), S100b (569.90 [524.10-783.80] vs. 763.40 [590.15-2713.00]; p=0.013), NSE (11.15 [6.26-14.91] vs. 13.93 [10.82-19.04]; p=0.021), nNOS (4.24 [3.34-12.85] vs. 12.82 [4.52-15.44]; p=0.028), and eNOS (64.83 [54.59-91.14] vs. 89.42 [61.19-228.40]; p=0.034) levels were lower in patients with three or more autonomic manifestations (n=9). No correlation was found between inflammation factors and clinical parameters of CH. Our results support the involvement of the IL-1β system in attacks of CH. However, the components of the inflammasome complex are suppressed in the peripheral blood and do not appear to play a role in the pathophysiology of CH. These findings argue against a potential biomarker value of the inflammasome complex in CH.