Time course of anti-inflammatory effect of low-dose radiotherapy: correlation with TGF-beta(1) expression

Abstract

Background and purpose: 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.

Materials and 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.