Effect of selective inhibitors of inflammation on oral mucositis: preclinical studies.
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-alpha or COX-2 on the epithelial radiation response in the mouse tongue model.


METHODS
Daily fractionated irradiation was given with 5 x 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-alpha 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-alpha 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-alpha or COX-2 are not relevant for the epithelial radiation response of oral mucosa.
Haagen
Julia
J
Dept. of Radiotherapy and Radiation Oncology, Medical faculty Carl Gustav Carus, University of Technology Dresden, Germany. Julia.Haagen@tu-dresden.de
Krohn
Hanna
H
Röllig
Sophie
S
Schmidt
Margret
M
Wolfram
Kathrin
K
Dörr
Wolfgang
W
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000068579:Celecoxib; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D005260:Female; D007249:Inflammation / Q000209:etiology / Q000517:prevention & control; D000069285:Infliximab; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009061:Mouth Mucosa / Q000473:pathology / Q000528:radiation effects; D011336:Probability; D011720:Pyrazoles / Q000494:pharmacology*; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000473:pathology; D011897:Random Allocation; D012016:Reference Values; D013280:Stomatitis / Q000188:drug therapy* / Q000209:etiology; D013449:Sulfonamides / Q000494:pharmacology*; D014059:Tongue / Q000187:drug effects / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000911:Antibodies, Monoclonal; D052246:Cyclooxygenase 2 Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068579:Celecoxib