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


METHODS
Thirty 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-1beta, IL-6 and TNF in the jejunum and colon. Protein expression of IL-1beta, IL-6 and TNF in the intestinal epithelium was investigated using qualitative immunohistochemistry.


RESULTS
Radiotherapy-induced sub-acute damage was associated with significantly upregulated IL-1beta, 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.


CONCLUSIONS
Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.
Ong
Zhi Yi
ZY
School of Medicine, University of Adelaide, Adelaide, South Australia.
Gibson
Rachel J
RJ
Bowen
Joanne M
JM
Stringer
Andrea M
AM
Darby
Jocelyn M
JM
Logan
Richard M
RM
Yeoh
Ann Sj
AS
Keefe
Dorothy M
DM
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis*; D005260:Female; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology*; D007413:Intestinal Mucosa / Q000276:immunology / Q000473:pathology / Q000528:radiation effects*; D052016:Mucositis / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D012333:RNA, Messenger / Q000032:analysis; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D012333:RNA, Messenger