PURPOSE: The aim of this study was to determine the effects of low-dose radiotherapy (LD-RT) on the inflammatory response and to characterize the potential mechanisms underlying these effects. METHODS AND MATERIALS: Mice were irradiated with 0.1, 0.3, 0.6 Gy, or sham radiation before lipopolysaccharide (LPS) challenge. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy. Intercellular adhesion molecule-1 (ICAM-1) expression was determined using radiolabeled antibodies 5 h after irradiation. Production of transforming growth factor-beta1 (TGF-beta1) was measured by enzyme-linked immunosorbent assay and its in vivo functional relevance by immunoneutralization. RESULTS: Compared with vehicle treated animals, LPS induced a marked increase in leukocyte adhesion (0.13+/-0.59 vs. 5.89+/-1.03, p<0.0001) in intestinal venules. The number of adherent leukocytes was significantly reduced by the 3 doses of LD-RT tested; the highest inhibition was observed with 0.3 Gy (0.66+/-1.96, p<0.0001). LPS-induced ICAM-1 upregulation was not modified by LD-RT. Circulating levels of TGF-beta1 were significantly increased in response to LD-RT in controls and LPS challenged animals. Neutralization of TGF-beta1 partially restored LPS-induced adhesion (4.83+/-1.41, p<0.05). CONCLUSIONS: LD-RT has a significant anti-inflammatory effect, inhibiting leukocyte recruitment, which is maximal at 0.3 Gy. This effect results in part from increased TGF-beta1 production and is not related to modulation of ICAM-1 expression.
PURPOSE: The aim of this study was to determine the effects of low-dose radiotherapy (LD-RT) on the inflammatory response and to characterize the potential mechanisms underlying these effects. METHODS AND MATERIALS: Mice were irradiated with 0.1, 0.3, 0.6 Gy, or sham radiation before lipopolysaccharide (LPS) challenge. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy. Intercellular adhesion molecule-1 (ICAM-1) expression was determined using radiolabeled antibodies 5 h after irradiation. Production of transforming growth factor-beta1 (TGF-beta1) was measured by enzyme-linked immunosorbent assay and its in vivo functional relevance by immunoneutralization. RESULTS: Compared with vehicle treated animals, LPS induced a marked increase in leukocyte adhesion (0.13+/-0.59 vs. 5.89+/-1.03, p<0.0001) in intestinal venules. The number of adherent leukocytes was significantly reduced by the 3 doses of LD-RT tested; the highest inhibition was observed with 0.3 Gy (0.66+/-1.96, p<0.0001). LPS-induced ICAM-1 upregulation was not modified by LD-RT. Circulating levels of TGF-beta1 were significantly increased in response to LD-RT in controls and LPS challenged animals. Neutralization of TGF-beta1 partially restored LPS-induced adhesion (4.83+/-1.41, p<0.05). CONCLUSIONS: LD-RT has a significant anti-inflammatory effect, inhibiting leukocyte recruitment, which is maximal at 0.3 Gy. This effect results in part from increased TGF-beta1 production and is not related to modulation of ICAM-1 expression.
Authors: Elisabet Rodríguez-Tomàs; Johana C Acosta; Laura Torres-Royo; Gabriel De Febrer; Gerard Baiges-Gaya; Helena Castañé; Andrea Jiménez; Carlos Vasco; Pablo Araguas; Junior Gómez; Bárbara Malave; Miguel Árquez; David Calderón; Berta Piqué; Manel Algara; Ángel Montero; Josep M Simó; Xavier Gabaldó-Barrios; Sebastià Sabater; Jordi Camps; Jorge Joven; Meritxell Arenas Journal: Antioxidants (Basel) Date: 2022-06-16
Authors: Franz Rödel; Benjamin Frey; Katrin Manda; Guido Hildebrandt; Stephanie Hehlgans; Ludwig Keilholz; M Heinrich Seegenschmiedt; Udo S Gaipl; Claus Rödel Journal: Front Oncol Date: 2012-09-25 Impact factor: 6.244