Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring.
OBJECTIVE
Beside its efficacy in cancer treatment, radiotherapy induces degeneration of healthy tissues within the irradiated area. The aim of this study was to analyze the variations of proinflammatory (IL-1α, IL-2, IL-6, TNF-α, IFN-γ), profibrotic (TGF-β1), proangiogneic (VEGF) and stem cell mobilizing (GM-CSF) cytokines and growth factors in an animal model of radiation-induced tissue degeneration.


METHODS
24 rats were irradiated unilaterally on the hindlimb at a monodose of 30 Gy. Six weeks (n=8), 6 months (n=8) and 1 year (n=8) after irradiation the mediators expression in skin and muscle were analyzed using Western blot and the Bio-Plex® protein array (BPA) technology. Additional histological severity for fibrosis, inflammation, vascularity and cellularity alterations scoring was defined from histology and immnunohistochemistry analyses.


RESULTS
A significant increase of histological severity scoring was found in irradiated tissue. Skin tissues were more radio-sensitive than muscle. A high level of TGF-β1 expression was found throughout the study and a significant relation was evidenced between TGF-β1 expression and fibrosis scoring. Irradiated tissue showed a chronic inflammation (IL-2 and TNF-α significantly increased). Moreover a persistent expression of GM-CSF and VEGF was found in all irradiated tissues. The vascular score was related to TGF-β1 expression and the cellular alterations score was significantly related with the level of IL-2, VEGF and GM-CSF.


CONCLUSIONS
The results achieved in the present study underline the complexity and multiplicity of radio-induced alterations of cytokine network. It offers many perspectives of development, for the comprehension of the mechanisms of late injuries or for the histological and molecular evaluation of the mode of action and the efficacy of rehabilitation techniques.
EA4421 SiGReTO Nancy University, Faculty of Medicine, Vandoeuvre-lès-Nancy, France.
Patrice
P
Gallet
Bérengère
B
Phulpin
Jean-Louis
JL
Merlin
Agnès
A
Leroux
Pierre
P
Bravetti
Hinda
H
Mecellem
Nguyen
N
Tran
Gilles
G
Dolivet
D000818:Animals; D015153:Blotting, Western; D016207:Cytokines / Q000378:metabolism*; D006614:Hindlimb / Q000528:radiation effects; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar
D016207:Cytokines; D036341:Intercellular Signaling Peptides and Proteins