Effect of recombinant human keratinocyte growth factor (&#x0394;23rHuKGF, Palifermin) on inflammatory and immune changes in mouse tongue during fractionated irradiation.
OBJECTIVE
A significant reduction in the incidence of radiation-induced oral mucositis by Palifermin has been demonstrated. The underlying mechanisms, however, remain unclear. The aim of the present study was to assess the effect of Palifermin on inflammatory and immune processes during fractionated irradiation in mouse tongue.


METHODS
Fractionated irradiation, 10 x 3 Gy in two weeks, was given to the snout of the animals. In one group, a single injection of Palifermin (15 mg/kg, s.c.) was given one day before the onset of radiotherapy. Groups of mice (n = 3) were sacrificed from day 1-16 after the start of irradiation. Vasodilatation, endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and the number of CD105-positive (CD105(+)) macrophages were assessed.


RESULTS
Compared to untreated control tissue, irradiation resulted in a significant vasodilatation and an increase in endothelial ICAM-1 staining intensity during the entire study period. Additionally, a significant increase in the number of CD105(+) macrophages was detected. In contrast, with Palifermin treatment before irradiation, none of these changes were found within the first 10 days.


CONCLUSIONS
Palifermin pre-treatment resulted in a long-lasting inhibition of radiation-induced inflammatory and immune changes in mouse tongue. This may contribute to the protective effect of this growth factor.
Jaal
Jana
J
Department of Radiotherapy and Oncological Therapy, Clinic of Haematology and Oncology, Tartu University Hospital, Estonia. Jana.Jaal@kliinikum.ee
Richter
Caroline
C
Dörr
Wolfgang
W
D000818:Animals; D002452:Cell Count; D019583:Dose Fractionation, Radiation; D000071063:Endoglin; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D005260:Female; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology* / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D011833:Radiation Injuries, Experimental / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology* / Q000627:therapeutic use; D013280:Stomatitis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D014059:Tongue / Q000098:blood supply / Q000187:drug effects* / Q000276:immunology / Q000528:radiation effects*; D014664:Vasodilation / Q000187:drug effects / Q000528:radiation effects
D000071063:Endoglin; C502004:Eng protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; D018799:Intercellular Adhesion Molecule-1