MECHANISMS OF THE ANTIINFLAMMATORY ACTIVITY OF LOW-DOSE RADIATION-THERAPY

Purpose: To investigate the hypothesis that modulation of the function of activated macrophages is one of the mechanisms of the clinically o bserved anti-inflammatory and analgesic efficacy of low-dose radiother apy in the treatment of a variety of painful joint diseases with total doses between 1 and 6 Gy. Materials and methods: Metabolic activity, cell proliferation, reproductive integrity, nitric oxide (NO) producti on and inducible nitric oxide synthase (iNOS) expression by unstimulat ed or LPS/gamma-IFN-stimulated macrophages in vitro was investigated a t different times after radiation doses ranging from 0.3 Gy to 10 Gy. In vivo, chronic granulomatous air pouches were induced in mice and ei ther sham treated or irradiated with 2 Gy on day 2 or day 6, or with f ive daily doses of 0.5 Gy. On day 7, the iNOS expression was assessed by Western blot and localized by immuno-histochemistry in cryostat sec tions. Results: In stimulated macrophages, metabolic activity, prolife ration and reproductive integrity were not affected by radiation doses up to 10 Gy since they are apparently irreversible postmitotic cells. However, a dose-dependent modulation of the NO pathway was observed w ith significant inhibition by the low radiation doses used in anti-inf lammatory radiotherapy but with super-stimulation by the high radiatio n doses used in cancer therapy. Conclusions: The empirically based ant i-inflammatory radiotherapy of benign diseases appears to act through specific modulation of different pathways of inflammatory reactions su ch as the nitric oxide pathway in stimulated macrophages.