Hildebrandt G, Radlingmayr A, Rosenthal S, Rothe R, Jahns J, Hindemith M, Rödel F, Kamprad F
Department of Radiotherapy and Radiooncology, University of Leipzig, Stephanstrasse 9a, D-04103 Leipzig, Germany.
Int J Radiat Biol. 2003 Dec;79(12):993-1001. doi: 10.1080/09553000310001636639.
Low-dose radiotherapy (LD-RT) of arthritic joints applied during the peak of the acute inflammatory response improves the clinical and histomorphological development of adjuvant arthritis. The study was undertaken to investigate the cellular composition of the inflammatory infiltrate and the expression of the pro-inflammatory and anti-inflammatory enzymes, inducible nitric oxide synthase (iNOS), cyclo-oxygenase 2 (COX-2) and haem-oxygenase 1 (HO-1), in response to LD-RT.
Adjuvant arthritis in female Lewis rats was induced by intradermal injection of heat-inactivated mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham irradiated (group 1) or X-irradiated with either 5 x 1.0 Gy (group 2) or 5 x 0.5 Gy (group 3) from days 15 to 19 after induction (15 animals/group). On days 21 (n=12 joints/group) and 30 (n=18 joints/group), cryostat sections were analysed histologically and immunohistologically after specific staining for macrophages, iNOS, COX-2 and HO-1.
A total of 5 x 1.0 Gy or 5 x 0.5 Gy led to a significant reduction of clinical symptoms from days 21 to 29, and a highly significant reduction of cartilage and bone destruction on day 30. Macrophage-positive areas could be detected continuously throughout the periarticular infiltrate, and were slightly reduced after LD-RT on days 21 and 30. This reduction was more pronounced after 5 x 1.0 Gy. Following LD-RT, the iNOS score was reduced by about 45-50% on days 21 (p<0.05) and 30 (p<0.001). In contrast, the HO-1 score was increased by about 50% on days 21 (p=0.08) and 30 (p=0.03).
The clinically and histologically observed prevention of the progression of adjuvant arthritis after LD-RT given during the peak of the acute inflammatory response and the reduction of cartilage and bone destruction in the chronic phase appears to be related to the modulation of iNOS activity by low X-ray doses.
在急性炎症反应高峰期对关节炎关节进行低剂量放疗（LD-RT）可改善佐剂性关节炎的临床和组织形态学发展。本研究旨在调查炎症浸润的细胞组成以及促炎和抗炎酶（诱导型一氧化氮合酶（iNOS）、环氧化酶2（COX-2）和血红素加氧酶1（HO-1））对LD-RT的反应表达。
于第0天皮内注射热灭活结核分枝杆菌诱导雌性Lewis大鼠发生佐剂性关节炎。诱导后第15至19天，对两只患关节炎的后爪进行假照射（第1组）或分别用5×1.0 Gy（第2组）或5×0.5 Gy（第3组）进行X线照射（每组15只动物）。在第21天（每组12个关节）和第30天（每组18个关节），对巨噬细胞、iNOS、COX-2和HO-1进行特异性染色后，对冷冻切片进行组织学和免疫组织学分析。
5×1.0 Gy或5×0.5 Gy的照射导致第21至29天临床症状显著减轻，第30天软骨和骨破坏高度显著减轻。在整个关节周围浸润中可连续检测到巨噬细胞阳性区域，在第21天和第30天LD-RT后略有减少。5×1.0 Gy后这种减少更为明显。LD-RT后，第21天（p<0.05）和第30天（p<0.001）iNOS评分降低约45-50%。相比之下，第21天（p=0.08）和第30天（p=0.03）HO-1评分增加约50%。
在急性炎症反应高峰期给予LD-RT后，临床和组织学观察到的佐剂性关节炎进展的预防以及慢性期软骨和骨破坏的减少似乎与低剂量X线对iNOS活性的调节有关。
