Mechanisms of the anti-inflammatory activity of low-dose radiation therapy

Abstract

Purpose: To investigate the hypothesis that modulation of the function of activated macrophages is one of the mechanisms of the clinically observed anti-inflammatory and analgesic efficacy of low-dose radiotherapy in the treatment of a variety of painful joint diseases with total doses between 1 and 6Gy. Materials and methods: Metabolic activity, cell proliferation, reproductive integrity, nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression by unstimulated or LPS/ gamma -IFN-stimulated macrophages in vitro was investigated at different times after radiation doses ranging from 0.3Gy to 10Gy. In vivo, chronic granulomatous air pouches were induced in mice and either sham treated or irradiated with 2Gy on day 2 or day 6, or with five daily doses of 0.5Gy. On day 7, the iNOS expression was assessed by Western blot and localized by immuno-histochemistry in cryostat sections. Results: In stimulated macrophages, metabolic activity, proliferation and reproductive integrity were not a ffected by radiation doses up to 10Gy since they are apparently irreversible postmitotic cells. However, a dose-dependent modulation of the NO pathway was observed with significant inhibition by the low radiation doses used in anti-inflammatory radiotherapy but with super-stimulation by the high radiation doses used in cancer therapy. Conclusions: The empirically based anti-inflammatory radiotherapy of benign diseases appears to act through specific modulation of different pathways of inflammatory reactions such as the nitric oxide pathway in stimulated macrophages.