Effect of selective inhibitors of inflammation on oral mucositis: Preclinical studies

• Published in: Radiotherapy and oncology Vol. 92; no. 3; pp. 472 - 476
• Main Authors: Haagen, Julia, Krohn, Hanna, Röllig, Sophie, Schmidt, Margret, Wolfram, Kathrin, Dörr, Wolfgang
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.09.2009
• Subjects: Animal model; Animals; Anti-inflammation; Antibodies, Monoclonal - pharmacology; Celecoxib; Cyclooxygenase 2 Inhibitors - pharmacology; Cyclooxygenase-2; Disease Models, Animal; Dose Fractionation; Dose-Response Relationship, Drug; Dose-Response Relationship, Radiation; Female; Fractionated irradiation; Hematology, Oncology and Palliative Medicine; Inflammation - etiology; Inflammation - prevention & control; Infliximab; Male; Mice; Mice, Inbred C3H; Mouth Mucosa - pathology; Mouth Mucosa - radiation effects; Oral mucositis; Probability; Pyrazoles - pharmacology; Radiation Injuries, Experimental - drug therapy; Radiation Injuries, Experimental - pathology; Random Allocation; Reference Values; Stomatitis - drug therapy; Stomatitis - etiology; Sulfonamides - pharmacology; Tongue - drug effects; Tongue - radiation effects; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor necrosis factor-α; Animal model; Oral mucositis; Fractionated irradiation; Tumor necrosis factor-α; Cyclooxygenase-2; Anti-inflammation
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2009.06.006

Abstract Objective Oral mucositis is a severe, dose-limiting side effect of radio(chemo)therapy for head and neck tumors. The epithelial radiation response (ulceration) is accompanied by inflammatory changes. Their interaction with the epithelial processes remains unclear. The present study was initiated to determine the effect of inhibition of TNF-α or COX-2 on the epithelial radiation response in the mouse tongue model. Methods Daily fractionated irradiation was given with 5 × 3 Gy/week over one (days 0–4) or two weeks (days 0–4, 7–11). Each protocol was terminated by graded test doses (5 dose groups, 10 animals each) to a defined area of the lower tongue surface to generate full dose–effect curves for mucosal ulceration. A TNF-α inhibiting antibody (Infliximab) or a COX-2 inhibitor (Celecoxib) was administered. Results No effect of Infliximab or Celecoxib was found in any of the protocols. Isoeffective doses for ulcer induction were unchanged. Also, the time course of the response was largely unaffected. Conclusions Inhibition of TNF-α or COX-2, two dominating inflammatory pathways, did not result in modulation of the response of oral epithelium during fractionated irradiation. This suggests that the inflammatory changes mediated through TNF-α or COX-2 are not relevant for the epithelial radiation response of oral mucosa.