Age-Related Increase Of IL-33 In Non-Eosinophilic Nasal Polyps

RATIONALE: Interleukin (IL)-33 has been shown to play an important role in chronic rhinosinusitis (CRS) and is postulated to be key in the development of nasal polyps (NP). Since the prevalence of NP increases with age, we explored the putative role of IL-33 in both elderly NP patients and in a murine model of NP.

METHODS: Sinonasal tissues were obtained during endoscopic sinus surgery from subjects with CRS and from young (2 months) and old (24 months) mice. Levels of IL-33 protein were measured using multiplex assay and issues from both groups of mice were examined with H&E and PAS staining. The effects of an anti-IL-33 antibody was investigated in the murine model of CRS and NP.

RESULTS: Goblet cell hyperplasia was increased in the elderly (≥65 old) compared to non-elderly healthy human control subjects (<50), and this was more prominent in NP. Levels of IL-33 were elevated in subjects with CRS compared with normal controls, and were higher in non-eosinophilic NP compared with eosinophilic NP (1.1 vs 0.6 ng/mg, p<0.01). There was a significant positive correlation between IL-33 levels and age (r=0.49, p=0.012). Similarly, there was sinonasal goblet cell hyperplasia in aged mice compared to young mice. Goblet cell hyperplasia was also significantly increased in older CRS/NP mice compared to control mice. Anti-IL-33 treatment markedly reduced goblet cell hyperplasia in these mice.

CONCLUSIONS: These data suggest that IL-33 is an important mediator and target for non-eosinophilic NP, especially in the elderly.