Mechanisms of the anti-inflammatory activity of low-dose radiation therapy.
OBJECTIVE
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 6 Gy.


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 0.3 Gy to 10 Gy. In vivo, chronic granulomatous air pouches were induced in mice and either sham treated or irradiated with 2 Gy on day 2 or day 6, or with five daily doses of 0.5 Gy. 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 affected by radiation doses up to 10 Gy since they are apparently irreversible post-mitotic 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.
Hildebrandt
G
G
Department of Radiation Biology, Saint Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
Seed
M P
MP
Freemantle
C N
CN
Alam
C A
CA
Colville-Nash
P R
PR
Trott
K R
KR
D000818:Animals; D002455:Cell Division; D002460:Cell Line / Q000528:radiation effects; D002470:Cell Survival; D002478:Cells, Cultured; D004307:Dose-Response Relationship, Radiation; D005260:Female; D015870:Gene Expression / Q000528:radiation effects; D006099:Granuloma / Q000201:enzymology; D007150:Immunohistochemistry; D007249:Inflammation / Q000532:radiotherapy; D007371:Interferon-gamma; D008070:Lipopolysaccharides; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D019001:Nitric Oxide Synthase / Q000032:analysis; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000032:analysis; D011879:Radiotherapy Dosage; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D008070:Lipopolysaccharides; D009573:Nitrites; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse