Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice.
OBJECTIVE
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
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.
Arenas
Meritxell
M
Department of Radiation Oncology, Hospital Clínic de Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Gil
Fèlix
F
Gironella
Meritxell
M
Hernández
Víctor
V
Jorcano
Sandra
S
Biete
Albert
A
Piqué
Josep M
JM
Panés
Julián
J
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects / Q000528:radiation effects; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D004730:Endothelium, Vascular; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000532:radiotherapy*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007958:Leukocyte Count; D007962:Leukocytes / Q000187:drug effects / Q000528:radiation effects*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D011879:Radiotherapy Dosage; D015854:Up-Regulation / Q000187:drug effects; D014699:Venules
D008070:Lipopolysaccharides; D018799:Intercellular Adhesion Molecule-1