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Interleukin 7 and Interleukin 15 interaction with the inflammation severity, predisposing factors and phenotype in chronic rhinosinusitis

Two major clinical phenotypes of chronic rhinosinusitis (CRS), with (CRSwNP) and without nasal polyps (CRSsNP) may show different regulation of inflammation, interplay between T cell subsets, remodelling, response to microbiome and association with predisposing comorbidities, like allergy, asthma and aspirin intolerance. IL-7 and IL-15 belong to common gamma chain cytokines, and are essentially involved in T cell homeostasis and proliferation. Several papers indicated that they might be involved in the immune response in asthma, however, their role in CRS was not evaluated. Our aim was to analyze interaction between IL-7 and IL-15 related to phenotypes and comorbidities. The study included 50 patients(both gender, age 18–60 years, 32 with CRSsNP, and 18 with CRSwNP), with CRS according to the EPOS criteria, who were submitted to endoscopic sinus surgery. Ethmoid sinus mucosa or nasal polyps were collected at surgery and immediately tissue homogenates were prepared and incubated with protease inhibitor. Assays (R&D System, Quantikine ELISA, UK) for interleukins IL-4, IL-5, IL-7, IL-15 and for interferon gamma (IFN-γ) employs the quantitative sandwich enzyme immunoassay technique. Tissue homogenates (n = 70) were analysed according to the manufacurer’s instructions (29 from non-allergic CRSsNP, 17 from allergic asthma patients, 11 from non-allergic asthma, 9 from allergic non-asthmatic CRSsNP and 4 from aspirin intolerant CRSwNP). Polyp and ethmoid sinus mucosa samples were taken in CRSwNP, and only ethmoid sinus mucosa from patients with CRSsNP, respectively, from the worse side according to imaging. IL-5 was significantly higher (mean 38.69 vs. 9.47 pg/ mL respectively), but IL-7 (0.1397 vs. 0.2638 pg/mL, respectively), and IFN-γ (22.44 vs. 41.71 pg/mL, respectively) significantly lower in samples from CRSwNP, and these differences were also significant when asthmatic were compared to non-asthmatic, irrespective of phenotype and sensitization. Interestingly, IFN-γ was significantly higher in patients with allergic sensitization, while IL-4 was significantly higher in patients with ASA intolerance. IL-15 significantly correlated with IL-7 (rho 0.44), IL-4 (rho 0.31) and IFN-γ significantly with IL-4 (rho 0.51). IL-7 and IL-15 are significantly upregulated in CRSsNP compared to CRSwNP and in non-asthmatics compared to asthmatics.

IL-7 ; IL-15 ; chronic rhinosinusitis ; nasal polyps ; T cell subset

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