Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice
- Department of Radiation Oncology, Hospital Clinic de Barcelona, Institut de Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona (Spain)
- Department of Gastroenterology, Hospital Clinic de Barcelona, Institut de Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona (Spain)
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-{beta}{sub 1} (TGF-{beta}{sub 1}) 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-{beta}{sub 1} were significantly increased in response to LD-RT in controls and LPS challenged animals. Neutralization of TGF-{beta}{sub 1} 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-{beta}{sub 1} production and is not related to modulation of ICAM-1 expression.
- OSTI ID:
- 20850135
- Journal Information:
- International Journal of Radiation Oncology, Biology and Physics, Vol. 66, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2006.06.004; PII: S0360-3016(06)00982-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0360-3016
- Country of Publication:
- United States
- Language:
- English
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