Expression and Clinical Significance of IL-33 and IL-25 in Post-Irradiation Otitis Media with Effusion.

PURPOSE

This study investigates IL-33 and IL-25 expression in post-radiation otitis media with effusion (POME), along with classic oxidative stress markers (MDA and SOD), to investigate radiation-induced oxidative stress and its association with ILC2-mediated chronic inflammation, providing basis for targeted therapies.

METHODS

Middle ear effusions (MEE) were collected from 35 irradiated nasopharyngeal carcinoma patients with otitis media with effusion (POME, 43 ears) and 20 non-irradiated conventional chronic otitis media with effusion (CCOME, 20 ears) patients. IL-33, IL-25, IL-6, SOD, and MDA levels were measured by ELISA. Eustachian tube function was evaluated using the Endoscopic Evaluation of the Eustachian Tube (3ET) scoring system.

RESULTS

Comparative analysis revealed distinct molecular profiles between POME and CCOME, with POME showing significantly reduced IL-33 levels (p=0.046) but elevated SOD activity (p=0.015), along with a non-significant trend toward higher MDA (p=0.083). Temporal analysis demonstrated peak expression of both IL-25 and IL-33 at 6 months post-radiation. Correlation studies identified significant associations between IL-33 (r=0.391) and IL-6, as well as between IL-25 (r=0.483) and IL-6 (both p<0.01). Clinically, IL-25 levels showed positive correlation with 3ET endoscopic scores (r=0.407, p=0.021) and were significantly reduced following tympanostomy tube placement (p=0.024). Notably, no direct correlation was observed between IL-33 and IL-25 (p>0.05), nor were any significant associations found with allergic comorbidities (all p>0.05).

CONCLUSION

IL-33 and IL-25 synergistically drive ILC2-mediated chronic inflammation in radiation-induced OME, with IL-25 emerging as a biomarker for radiotherapy-associated Eustachian tube dysfunction. The 6-month cytokine surge post-radiation highlights a therapeutic window for targeted interventions to mitigate long-term complications.