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Radiation Oncology
Published in: Radiation Oncology 1/2010

Open Access 01-12-2010 | Research

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

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

Published in: Radiation Oncology | Issue 1/2010

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Abstract

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-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.

Results

Radiotherapy-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.

Conclusions

Pro-inflammatory cytokines play a key role in radiotherapy-induced gastrointestinal mucositis in the sub-acute onset setting.
Appendix
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Literature
1.
Avritscher EB, Cooksley CD, Elting LS: Scope and epidemiology of cancer therapy-induced oral and gastrointestinal mucositis. Semin Oncol Nurs 2004, 20: 3-10. 10.1053/j.soncn.2003.10.002CrossRefPubMed
2.
Keefe DM, Gibson RJ, Hauer-Jensen M: Gastrointestinal mucositis. Semin Oncol Nurs 2004, 20: 38-47. 10.1053/j.soncn.2003.10.007CrossRefPubMed
3.
Keefe DM, Schubert MM, Elting LS, Sonis ST, Epstein JB, Raber-Durlacher JE, Migliorati CA, McGuire DB, Hutchins RD, Peterson DE: Updated clinical practice guidelines for the prevention and treatment of mucositis. Cancer 2007, 109: 820-831. 10.1002/cncr.22484CrossRefPubMed
4.
Pico JL, Avila-Garavito A, Naccache P: Mucositis: Its Occurrence, Consequences, and Treatment in the Oncology Setting. Oncologist 1998, 3: 446-451.PubMed
5.
6.
Logan RM, Gibson RJ, Bowen JM, Stringer AM, Sonis ST, Keefe DM: Characterisation of mucosal changes in the alimentary tract following administration of irinotecan: implications for the pathobiology of mucositis. Cancer Chemother Pharmacol 2008,62(1):33-41. 10.1007/s00280-007-0570-0CrossRefPubMed
7.
Cho SA, Park JH, Seok SH, Juhn JH, Kim SJ, Ji HJ, Choo YS, Park JH: Effect of granulocyte macrophage-colony stimulating factor (GM-CSF) on 5-FU-induced ulcerative mucositis in hamster buccal pouches. Exp Toxicol Pathol 2006, 57: 321-328. 10.1016/j.etp.2005.09.006CrossRefPubMed
8.
Sonis ST, Peterson RL, Edwards LJ, Lucey CA, Wang L, Mason L, Login G, Ymamkawa M, Moses G, Bouchard P, Hayes LL, Bedrosian C, Dorner AJ: Defining mechanisms of action of interleukin-11 on the progression of radiation-induced oral mucositis in hamsters. Oral Oncol 2000, 36: 373-381. 10.1016/S1368-8375(00)00012-9CrossRefPubMed
9.
Blijlevens N, Sonis S: Palifermin (recombinant keratinocyte growth factor-1): a pleiotropic growth factor with multiple biological activities in preventing chemotherapy - and radiotherapy-induced mucositis. Ann Oncol 2007, 18: 817-826. 10.1093/annonc/mdl332CrossRefPubMed
10.
Gibson RJ, Keefe DM, Thompson FM, Clarke JM, Goland GJ, Cummins AG: Effect of interleukin-11 on ameliorating intestinal damage after methotrexate treatment of breast cancer in rats. Dig Dis Sci 2002, 47: 2751-2757. 10.1023/A:1021061306913CrossRefPubMed
11.
von Bultzingslowen I, Brennan MT, Spijkervet FK, Logan R, Stringer A, Raber-Durlacher JE, Keefe D: Growth factors and cytokines in the prevention and treatment of oral and gastrointestinal mucositis. Support Care Cancer 2006, 14: 519-527. 10.1007/s00520-006-0052-7CrossRefPubMed
12.
Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, Bekele BN, Raber-Durlacher J, Donnelly JP, Rubenstein EB: Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004, 100: 1995-2025. 10.1002/cncr.20162CrossRefPubMed
13.
Yeoh AS, Gibson RJ, Yeoh EE, Bowen JM, Stringer AM, Giam KA, Keefe DM: A novel animal model to investigate fractionated radiotherapy-induced alimentary mucositis: the role of apoptosis, p53, nuclear factor-kappaB, COX-1, and COX-2. Mol Cancer Ther 2007, 6: 2319-2327. 10.1158/1535-7163.MCT-07-0113CrossRefPubMed
14.
Hovdenak N, Fajardo LF, Hauer-Jensen M: Acute radiation proctitis: a sequential clinicopathologic study during pelvic radiotherapy. Int J Radiation Oncology Biol Phys 2000,48(4):1111-1117. 10.1016/S0360-3016(00)00744-6CrossRef
15.
Stringer AM, Gibson RJ, Logan RM, Bowen JM, Yeoh ASJ, Laurence J, Keefe DMK: Irinotecan-induced mucositis is associated with changes in intestinal mucins. Cancer Chemother Pharmacol 2009,64(1):123-132. 10.1007/s00280-008-0855-yCrossRefPubMed
16.
Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25: 402-408. 10.1006/meth.2001.1262CrossRefPubMed
17.
Yeoh AS, Bowen JM, Gibson RJ, Keefe DM: Nuclear factor kappaB (NFkappaB) and cyclooxygenase-2 (Cox-2) expression in the irradiated colorectum is associated with subsequent histopathological changes. Int J Radiat Oncol Biol Phys 2005, 63: 1295-1303. 10.1016/j.ijrobp.2005.04.041CrossRefPubMed
18.
Trott KR, Kamprad F: Radiobiological mechanisms of anti-inflammatory radiotherapy. Radiother Oncol 1999, 51: 197-203. 10.1016/S0167-8140(99)00066-3CrossRefPubMed
19.
Dent P, Yacoub A, Fisher PB, Hagan MP, Grant S: MAPK pathways in radiation responses. Oncogene 2003,22(37):5885-5896. 10.1038/sj.onc.1206701CrossRefPubMed
20.
Papa S, Bubici C, Zazzeroni F, Pham CG, Kuntzen C, Knbb JR, Dean K, Franzoso G: The NF-κB-mediated control of the JNK cascade in the antagonism of programmed cell death in health and disease. Cell Death Diff 2006, 13: 712-729. 10.1038/sj.cdd.4401865CrossRef
21.
Hall EJ: Radiobiology for the radiologist. Philadelphia: Lippincott Williams & Wilkins; 2000.
22.
Gibson RJ, Bowen JM, Cummins AG, Keefe DM: Relationship between dose of methotrexate, apoptosis, p53/p21 expression and intestinal crypt proliferation in the rat. Clin Exp Med 2005, 4: 188-195. 10.1007/s10238-004-0055-yCrossRefPubMed
23.
Gibson RJ, Bowen JM, Inglis MR, Cummins AG, Keefe DM: Irinotecan causes severe small intestinal damage, as well as colonic damage, in the rat with implanted breast cancer. J Gastroenterol Hepatol 2003, 18: 1095-1100. 10.1046/j.1440-1746.2003.03136.xCrossRefPubMed
Metadata
Title
Pro-inflammatory cytokines play a key role in the development of radiotherapy-induced gastrointestinal mucositis
Authors
Zhi Yi Ong
Rachel J Gibson
Joanne M Bowen
Andrea M Stringer
Jocelyn M Darby
Richard M Logan
Ann SJ Yeoh
Dorothy M Keefe
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Radiation Oncology / Issue 1/2010
Electronic ISSN: 1748-717X
DOI
https://doi.org/10.1186/1748-717X-5-22

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