Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different fractionation schedules.
ABSTRACT Low-dose radiotherapy is widely accepted as a very effective treatment option for inflammatory symptoms associated with painful degenerative joint disorders. Radiation doses and fractionation schedules in practical use are empirical and mainly based on clinical observations. Experimental data are rare. The efficacy of low-dose X-irradiation on adjuvant induced arthritis in rats using different fractionation schemes was investigated in vivo, in order to explore whether there is a dose and fractionation dependence.
Adjuvant arthritis in female Lewis rats (n = 128) was induced by intradermal injection of heat-inactivated Mycobacterium tuberculosis on day 0. Both arthritic hind paws were sham-irradiated (group 1: days 10-14; group 2: days 15-19; group 3: days 22-26) or X-irradiated with either 5 x 1.0 Gy (group 4: days 10-14; group 6: days 15-19; group 8: days 22-26; group 10: days 10, 12, 14, 16, and 18) or 5 x 0.5 Gy (group 5: days 10-14; group 7: days 15-19; group 9: days 22-26; group 11: days 10, 12, 14, 16, and 18; group 12: days 10-14 and 22-26). The clinical parameters arthritis score (AS), hind paw volume (HPV), and body weight were determined.
A significant decrease of the clinical arthritis parameters was observed following 5 x 0.5 Gy or 5 x 1.0 Gy during the acute maximum of the inflammatory response (days 15-19). The most pronounced treatment effect was reached after two daily fractionated series of 5 x 0.5 Gy with an early treatment onset (days 10-14) and repetition in interval (days 22-26). After the application of 5 x 1.0 Gy on days 10-14 or in a protracted scheme (days 10, 12, 14, 16, and 18), only a nonsignificant positive trend could be detected. Daily fractionated X-irradiation in the chronic phase of adjuvant arthritis (days 22-26) did not show any positive clinical effect.
Low-dose radiotherapy is able to prevent a full-blown arthritic reaction if given during the florid phase of adjuvant arthritis. Two series of 5 x 0.5 Gy with an early treatment onset (days 10-14) and repetition in interval (days 22-26) were the most effective treatment schedule in this experimental study.
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ABSTRACT: We reviewed the beneficial or harmful effects of low-dose ionizing radiation on several diseases based on a search of the literature. The attenuation of autoimmune manifestations in animal disease models irradiated with low-dose γ-rays was previously reported by several research groups, whereas the exacerbation of allergic manifestations was described by others. Based on a detailed examination of the literature, we divided animal disease models into two groups: one group consisting of collagen-induced arthritis (CIA), experimental encephalomyelitis (EAE), and systemic lupus erythematosus, the pathologies of which were attenuated by low-dose irradiation, and another group consisting of atopic dermatitis, asthma, and Hashimoto's thyroiditis, the pathologies of which were exacerbated by low-dose irradiation. The same biological indicators, such as cytokine levels and T-cell subpopulations, were examined in these studies. Low-dose irradiation reduced inter-feron (IFN)-gamma (γ) and interleukin (IL)-6 levels and increased IL-5 levels and the percentage of CD4(+)CD25(+)Foxp3(+)Treg cells in almost all immunological disease cases examined. Variations in these biological indicators were attributed to the attenuation or exacerbation of the disease's manifestation. We concluded that autoimmune diseases caused by autoantibodies were attenuated by low-dose irradiation, whereas diseases caused by antibodies against external antigens, such as atopic dermatitis, were exacerbated.Dose-Response 07/2014; 12(3):429-65. · 1.50 Impact Factor
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ABSTRACT: Langerhans Cell Histiocytosis (LCH) represents a rare benign disorder, previously designated as "Histiocytosis X", "Type II Histiocytosis" or "Langerhans Cell Granulomatosis". Clinical presentation includes osteolysis, ulcerations of skin and soft tissues but also involvement of the CNS is described.Because treatment concepts are not well defined the German Cooperative Group on Radiotherapy for Benign Diseases performed a retrospective analysis.Methods and material: Eight closely cooperating centres collected patients' data of the past 45 years. As study endpoints disease free survival, recurrent disease, death and therapy related side effects were defined. A total of 80 patients with histologically proven LCH were irradiated within the past 45 years. According to the LCH classification of Greenberger et al. 37 patients had stage Ia, 21 patients stage Ib, 13 patients stage II and 9 patients stage IIIb and the median age was 29 years. The median Follow up was 54 months (range 9--134 months). A total of 39 patients had a surgical intervention and 23 patients a chemotherapy regimen.Radiation treatment was carried out with a median total dose of 15 Gy (range 3--50.4Gy). The median single fraction was 2 Gy (range 1.8-3 Gy).Overall, 77% patients achieved a complete remission and 12.5% achieved a partial remission. The long-term control rate reached 80%. Within an actuarial overall 5-year survival of 90% no radiogenic side and late effects >=EORTC/RTOG II[degree sign] were observed. In the present study a large collective of irradiated patients was analysed. Radiotherapy (RT) is a very effective and safe treatment option and even low RT doses show sufficient local control.Radiation Oncology 10/2013; 8(1):233. · 2.11 Impact Factor
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ABSTRACT: Purpose: To evaluate retrospectively the efficacy of low-dose radiotherapy in painful gonarthritis. METHODS: We assessed the medical records of 1037 patients with painful gonarthritis, who had undergone low-dose radiotherapy between 1981 and 2008. Subjective patient perception of response to irradiation as graded immediately or up to two months after completion of a radiotherapy series was evaluated and correlated with age, gender, radiological grading and the duration of symptoms before radiotherapy. Moreover, we performed a mail survey to obtain additional long-term follow-up information and received one hundred and six evaluable questionnaires. RESULTS: We assessed 1659 series of radiotherapy in 1037 patients. In 79.3% of the cases the patients experienced a slight, marked or complete pain relief immediately or up to two months after completion of radiotherapy. Gender, age and the duration of pain before radiotherapy did not have a significant influence on response to irradiation. In contrast, severe signs of osteoarthritis where associated with more effective pain relief. In more than 50% of the patients who reported a positive response to irradiation a sustained period of symptomatic improvement was observed. CONCLUSIONS: Our results confirm that low-dose radiotherapy is an effective treatment for painful osteoarthritis of the knee. In contrast to an earlier retrospective study, severe signs of osteoarthritis constituted a potential positive prognostic factor for response to irradiation. A randomized trial is urgently required to compare radiotherapy with other treatment modalities.Radiation Oncology 01/2013; 8(1):29. · 2.11 Impact Factor