Long-Term Alterations of Cytokines and Growth Factors Expression in Irradiated Tissues and Relation with Histological Severity Scoring

Abstract

PurposeBeside 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.Materials and Methods24 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.ResultsA 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.ConclusionThe 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.

Biomarkers Expression in Cervical Cancer and High Grade Squamous Intraepithelial Lesions

“…Besides VEGF, erythropoietin (Epo) is another of the best known hypoxia-regulated genes mediated by HIF-1 [25]. Epo is a glycoprotein hormone that stimulates erythropoiesis, which exerts its effect by stimulating growth, preventing apoptosis and inducing differentiation of red blood cell precursors.…”

Moyamoya Syndrome Associated With Gamma Knife Surgery for Cerebral Arteriovenous Malformation

“…Recently, radiation therapy was suggested to induce chronic oxidative stress and inflammation, 18) and irradiated tissue may undergo long-term changes in the expression of cytokines and growth factors. 5) The guidelines of research on intractable diseases of the Ministry of Health Labour and Welfare, Japan, suggest that inflammation leads to moyamoya syndrome. 14) Therefore, chronic inflammation due to GKS may have caused, in part, the formation of moyamoya vessels in this case.…”

Carence martiale fonctionnelle, inflammation et fatigue après radiothérapie

“…D'un point de vue histologique, quatre phénomènes sont impliqués dans les effets aigus et tardifs de la radiothérapie : inflammation, fibrose, altérations vasculaires et déplétion cellulaire [33].…”

“…De nombreuses études ont montré, dans des modèles animaux et chez les patients atteints de cancers, une libération de cytokines inflammatoires au cours de l'irradiation secondaire à la lyse cellulaire radio-induite [2- 11,33].…”