Reduced expression of inflammasome complex components in cluster headache.


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Şahin E., Karaaslan Z., Şanlı E., Timirci Kahraman Ö., Ulusoy C., Kocasoy Orhan E., ...Daha Fazla

Headache, cilt.62, sa.8, ss.967-976, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 62 Sayı: 8
  • Basım Tarihi: 2022
  • Doi Numarası: 10.1111/head.14334
  • Dergi Adı: Headache
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CINAHL, EMBASE, MEDLINE, Public Affairs Index, SportDiscus
  • Sayfa Sayıları: ss.967-976
  • İstanbul Üniversitesi Adresli: Evet

Özet

Background: The involvement of inflammation in the pathophysiology of cluster headache (CH) has been suggested, with a role implied for interleukin (IL)-1 beta. We aimed to measure peripheral blood expression levels of IL-1 beta-inducing systems, the inflammasome complex, and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) 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-1 beta, IL-18, and nitric oxide synthase isoforms), neuron-specific enolase, other inflammatory factors (NF-kappa B, 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-1 beta (2(-Delta Delta CT) median [25th-75th percentile], 0.96 [0.66-1.29 vs. 0.52 [0.43-0.73]) and NF-kappa B (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. Conclusion: Our results support the involvement of the IL-1 beta 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.