Characterization of IL-18 expression and release in the pathogenesis of chronic rhinosinusitis.
BACKGROUND
Interleukin-18 (IL-18) is a member of the IL-1 cytokine family that affects chronic inflammation. We sought to characterize IL-18 expression and investigate its release during chronic rhinosinusitis (CRS).


METHODS
The expression of IL-18 in nasal polyps (NPs) and uncinate tissues (UTs) from both CRS and non-CRS patients was examined via immunohistochemistry. After culturing dispersed NP cells (DNPCs) with or without various stimulations, IL-18 levels were measured in the culture supernatants. Furthermore, the effect of IL-18 neutralization on staphylococcus enterotoxin B (SEB)-induced cytokine production was also examined.


RESULTS
Similar expression of IL-18 in the epithelial layers was observed between the NPs and UTs. However, there was a significantly higher number of IL-18(+) cells in the lamina propria from NPs compared to UTs without CRS. This increased number was significantly correlated with the radiological severity of sinusitis and local eosinophilia. After the dispersion, IL-18 was spontaneously released by NP cells in a phase-dependent manner. While SEB, fungal antigens, and TLR agonists did not enhance the release, exposure to protease or one cycle of a freeze-and-thaw treatment did induce release of IL-18 from rested DNPCs. In addition, neutralization of IL-18 significantly suppressed SEB-induced IL-5, IL-13, and IFN-γ, but not IL-17A production.


CONCLUSIONS
These results suggest that the pro-inflammatory effect of IL-18 released by danger signals may be involved in the pathogenesis of CRS, which includes eosinophilic inflammation and NP formation, via the augmentation of both Th2- and Th1-associated cytokine production.
Department of Otolaryngology-Head and Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan. mokano@cc.okayama-u.ac.jp
Mitsuhiro
M
Okano
Tazuko
T
Fujiwara
Seiichiro
S
Makihara
Rumi
R
Fujiwara
Takaya
T
Higaki
Shin
S
Kariya
Yohei
Y
Noda
Takenori
T
Haruna
Kazunori
K
Nishizaki
D000328:Adult; D000368:Aged; D019138:Antibodies, Blocking / Q000494:pharmacology; D002478:Cells, Cultured; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004768:Enterotoxins / Q000276:immunology; D005260:Female; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D020382:Interleukin-18 / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology*; D009298:Nasal Polyps / Q000150:complications / Q000276:immunology*; D012220:Rhinitis / Q000150:complications / Q000276:immunology*; D012852:Sinusitis / Q000150:complications / Q000276:immunology*
D019138:Antibodies, Blocking; D016207:Cytokines; D004768:Enterotoxins; D020382:Interleukin-18; C031818:enterotoxin B, staphylococcal