Innate immune activity in radiation Proctitis

Radiation proctitis is a common and morbid complication of pelvic radiotherapy, yet its pathophysiological mechanisms remain incompletely understood. Preclinical models suggest that activation of the innate immune system, particularly the NF-kappaB signaling pathway, plays a key role in regulating intestinal responses to ionizing radiation. This study aimed to investigate the activation of innate immune responses in rectal mucosa during prostate radiotherapy and examine correlations with the development of acute proctitis.

A prospective observational study was conducted at University Hospital Galway, including 28 prostate cancer patients receiving external beam radiotherapy (74 Gy in 37 fractions). Clinical symptoms were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v3.0). Endoscopic examinations and rectal biopsies were performed at baseline (week 0) and post-treatment (week 6). Histological evaluation and immunohistochemistry for phospho-p65 NF-kappaB were used to assess mucosal injury and immune activation. Real-time PCR was performed to quantify the expression of NF-kappaB target cytokine genes (IL-1β, IL-6, IL-8, TNF-α).

There was a progressive increase in the frequency of proctitis symptoms, with significant elevations in endoscopic and histological scores from baseline to week 6 (P < 0.0001). NF-kappaB activation scores significantly increased post-radiotherapy (P < 0.0001), and a moderate positive correlation was observed between endoscopic scores and NF-kappaB activation (rho = 0.483, P = 0.009). While expression levels of target cytokine genes increased post-treatment, these changes did not reach statistical significance.

This study provides evidence of innate immune activation in the rectal mucosa during prostate radiotherapy, particularly via NF-kappaB signaling. These findings suggest that mucosal immune responses contribute to the development of radiation proctitis and highlight potential therapeutic targets to mitigate gastrointestinal toxicity.