Long-term alterations of cytokines and growth factors expression in irradiated tissues and relation with histological severity scoring. PLoS One 2011

Purpose: 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-1a, IL-2, IL-6, TNF-a, IFN-c), profibrotic (TGF-b1), proangiogneic (VEGF) and stem cell mobilizing (GM-CSF) cytokines and growth factors in an animal model of radiation-induced tissue degeneration. Materials and 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-PlexH 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-b1 expression was found throughout the study and a significant relation was evidenced between TGF-b1 expression and fibrosis scoring. Irradiated tissue showed a chronic inflammation (IL-2 and TNF-a significantly increased). Moreover a persistent expression of GM-CSF and VEGF was found in all irradiated tissues. The vascular score was related to TGF-b1 expression and the cellular alterations score was significantly related with the level o