Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis

Zhi Yi Ong,Dorothy M Keefe,Richard M Logan,Joanne M Bowen,Ann Sj Yeoh,Jocelyn M Darby,Rachel J Gibson,Andrea M Stringer

doi:10.1186/1748-717x-5-22

Zhi Yi Ong, Dorothy M Keefe + Show 6 more

Open Access

https://doi.org/10.1186/1748-717x-5-22

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Abstract

BackgroundMucositis is a toxic side effect of anti-cancer treatments and is a major focus in cancer research. Pro-inflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis. However, whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. Therefore, the aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity.MethodsThirty six female Dark Agouti rats were randomly assigned into groups and received 2.5 Gys abdominal radiotherapy three times a week over six weeks. Real time PCR was conducted to determine the relative change in mRNA expression of pro-inflammatory cytokines IL-1β, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1β, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry.ResultsRadiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1β, IL-6 and TNF mRNA levels in the jejunum and colon. The majority of pro-inflammatory cytokine protein expression in the jejunum and colon exhibited minimal change following fractionated radiotherapy.ConclusionsPro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.

Highlights

Mucositis is a debilitating side effect of cytotoxic chemotherapy (CT) and radiotherapy (RT)
IL-6 mRNA levels were increased in rats receiving 45 Gy of RT compared with all other doses
This study has shown for the first time, using the fractionated radiotherapy-induced mucositis rat model, that mRNA levels of pro-inflammatory cytokines, IL-1b, IL-6 and TNF, are significantly upregulated in the intestines following long term radiotherapy when compared to short term radiotherapy

Summary

Introduction

Mucositis is a debilitating side effect of cytotoxic chemotherapy (CT) and radiotherapy (RT). Palifermin and IL-11 have been reported to be successful in lowering the levels of pro-inflammatory cytokines in the development of mucositis [8,9,10,11]. They attenuate mucositis in animal models [8,9,10,11,12], supporting the current view that pro-inflammatory cytokines play a major role in the development of mucositis. Proinflammatory cytokines have previously been implicated in the pathophysiology of chemotherapy-induced gastrointestinal mucositis Whether they play a key role in the development of radiotherapy-induced gastrointestinal mucositis is still unknown. The aim of the present study was to characterise the expression of pro-inflammatory cytokines in the gastrointestinal tract using a rat model of fractionated radiotherapy-induced toxicity

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