Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-beta(1) expression.
OBJECTIVE
Low-dose radiotherapy (LD-RT) has a potent anti-inflammatory effect, and transforming growth factor (TGF)-beta(1) is a potential mediator of this effect. The objectives of this study were to characterize the in vivo effects of LD-RT on leukocyte recruitment over time, and its relationship with TGF-beta(1) production.


METHODS
Mice were submitted to abdominal irradiation with a dose of 0.3 Gy, or to sham radiation and studied 5, 24, 48 or 72 h after irradiation. Four hours before the study a proinflammatory stimulus consisting of LPS or placebo was administered. Leukocyte-endothelial cell interactions in intestinal venules were assessed using intravital microscopy. Circulating levels and intestinal tissue production of TGF-beta(1) were determined.


RESULTS
Compared to non-irradiated LPS-challenged group, the number of adherent leukocytes was significantly reduced 5, 24 and 48 h, but not 72 h after irradiation in LPS-challenged mice. Rolling leukocytes were significantly decreased at all time points analyzed. Plasma TGF-beta(1) levels were increased 5 and 24h after irradiation. Increased intestinal production during this period was corroborated by in vitro culture experiments.


CONCLUSIONS
LD-RT has a sustained inhibitory effect on leukocyte recruitment for 48 h, which is initially associated with an increase in TGF-beta(1) intestinal production.
Arenas
Meritxell
M
Department of Radiation Oncology, Hospital Clínic de Barcelona, University of Barcelona, Spain.
Gil
Fèlix
F
Gironella
Meritxell
M
Hernández
Víctor
V
Biete
Albert
A
Piqué
Josep M
JM
Panés
Julián
J
D000818:Animals; D002448:Cell Adhesion / Q000528:radiation effects; D002450:Cell Communication; D042783:Endothelial Cells / Q000528:radiation effects; D007958:Leukocyte Count; D036904:Leukocyte Rolling / Q000528:radiation effects; D007962:Leukocytes / Q000528:radiation effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D011879:Radiotherapy Dosage; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis* / Q000097:blood; D015854:Up-Regulation
D053773:Transforming Growth Factor beta1