Strahlentherapie und Onkologie

, Volume 188, Issue 11, pp 975–981 | Cite as

Anti-inflammatory effects of low-dose radiotherapy

Indications, dose, and radiobiological mechanisms involved
  • M. Arenas
  • S. Sabater
  • V. Hernández
  • A. Rovirosa
  • P.C. Lara
  • A. Biete
  • J. Panés
Review article

Abstract

Low-dose radiotherapy (LD-RT) has been used for several benign diseases, including arthrodegenerative and inflammatory pathologies. Despite its effectiveness in clinical practice, little is known about the mechanisms through which LD-RT modulates the various phases of the inflammatory response and about the optimal dose fractionation. The objective of this review is to deepen knowledge about the most effective LD-RT treatment schedule and radiobiological mechanisms underlying the anti-inflammatory effects of LD-RT in various in vitro experiments, in vivo studies, and clinical studies.

Keywords

Low-dose radiotherapy Leukocyte Endothelium Adhesion molecules Benign diseases 

Entzündungshemmende Effekte von niedrigdosierter Strahlentherapie

Indikationen, Dosis und zugrundeliegende radiobiologische Mechanismen

Zusammenfassung

Niedrigdosierte Strahlentherapie (LD-RT) wird für die Behandlung verschiedener gutartiger Erkrankungen, einschließlich für arthrodegenerative und entzündliche Erkrankungen verwendet. Obwohl diese in der Praxis effektiv sind, wissen wir noch sehr wenig über die zugrundeliegenden Mechanismen der entzündungshemmenden Wirkung und die optimale Dosisfraktionierung. Das Ziel des Artikels ist es, unser Wissen über LD-RT und die zugrundeliegenden entzündungshemmenden Effekte in verschiedenen In-vitro-Versuchen und In-vivo-Studien sowie in klinischen Studien zu vertiefen.

Schlüsselwörter

Niedrigdosierte Strahlentherapie Leukozyten Endothelium Adhäsionsmoleküle Gutartige Erkrankungen 

References

  1. 1.
    Adamietz B, Schulz-Wendtland R, Alibek S et al (2010) Calcifying tendonitis of the shoulder joint: predictive value of pretreatment sonography for the response to low-dose radiotherapy. Strahlenther Onkol 186(1):18–23PubMedCrossRefGoogle Scholar
  2. 2.
    Arenas M, Gil F, Gironella M et al (2006) Anti-inflammatory effects of low-dose radiotherapy in an experimental model of systemic inflammation in mice. Int J Radiat Oncol Biol Phys 66(2):560–567PubMedCrossRefGoogle Scholar
  3. 3.
    Arenas M, Gil F, Gironella M et al (2008) Time course of anti-inflammatory effect of low-dose radiotherapy. correlation with TGF-beta(1) expression. Radiother Oncol 86(3):399–406PubMedCrossRefGoogle Scholar
  4. 4.
    Betz N, Ott OJ, Adamietz B et al (2010) Radiotherapy in early-stage Dupuytre’s contracture. Long-terms results after 13 years. Strahlenther Onkol 186(1):82–90PubMedCrossRefGoogle Scholar
  5. 5.
    Brenner DJ, Sachs RK (2006) Estimating radiation-induced cancer risks at very low doses: rationale for using a linear no-threshold approach. Radiat Environ Biophys 44:253–256PubMedCrossRefGoogle Scholar
  6. 6.
    Broerse JJ, Jansen JTM, Seegenschmiedt MH (2004) Carcinogenic risks in radiotherapy of benign diseases for head to heel. Radiother Oncol 71(suppl 1):1CrossRefGoogle Scholar
  7. 7.
    Budras KD, Hartung K, Munzer BM (1986) Light and electron microscopy studies of the effect of roentgen irradiation on the synovial membrane of the inflamed knee joint. Berl Munch Tierarztl Wochenschr 99:148–152PubMedGoogle Scholar
  8. 8.
    Cannon B, Randolph JG, Murray JE (1959) Malignant irradiation for benign conditions. N Engl J Med 260:197–202PubMedCrossRefGoogle Scholar
  9. 9.
    Cardis E, Vrijheid M, Blettner M et al (2007) The 15-Country collaborative study of cancer risk among radiation workers in the nuclear industry: estimates of radiation-related cancer risks. Radiat Res 167:396–416PubMedCrossRefGoogle Scholar
  10. 10.
    Cardis E, Vrijheid M, Blettner M et al (2005) Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. BMJ 331:77PubMedCrossRefGoogle Scholar
  11. 11.
    Cohen BL (1994) Dose-response relationship for radiation carcinogenesis in the low-dose region. Int Arch Occup Environ Health 66:71–75PubMedCrossRefGoogle Scholar
  12. 12.
    Cohen BL (1995) How dangerous is low level radiation? Risk Anal 15:645–653PubMedCrossRefGoogle Scholar
  13. 13.
    Court-Brawn WM, Doll R (1965) Mortality from cancer and other causes after radiotherapy for ankylosing spondylitis. BMJ 2:1327–1332CrossRefGoogle Scholar
  14. 14.
    Crocker I (1999) Radiation therapy to prevent coronary artery restenosis. Semin Radiat Oncol 9:134–143PubMedCrossRefGoogle Scholar
  15. 15.
    Fischer U, Kamprad F, Koch F et al (1998) The effects of low-dose Co-60 irradiation on the course of aseptic arthritis in a rabbit knee joint. Strahlenther Onkol 174:633–639PubMedCrossRefGoogle Scholar
  16. 16.
    Gaipl US, Meister S, Lodermann B et al (2009) Activation-induced cell death and total Akt content of granulocytes show a biphasic course after low-dose rradiation. Autoimmunity 42:340–342PubMedCrossRefGoogle Scholar
  17. 17.
    Ghiassi-Nejad M, Mortazavi SM, Cameron JR et al (2002) Very high background radiation areas of Ramsar, Iran: preliminary biological studies. Health Phys 82:87–93PubMedCrossRefGoogle Scholar
  18. 18.
    Ghiassi-Nejad M, Zakeri F, Assaei RG, Kariminia A (2004) Long-term immune and cytogenetic effects of high level natural radiation on Ramsar inhabitants in Iran. J Environ Radioact 74:107–116PubMedCrossRefGoogle Scholar
  19. 19.
    Glatzel M, Fröhlich D, Bäsecke S (2004) Analgesic radiotherapy for osteoarthrosis of digital joints and rhizarthrosis. Radiother Oncol 71:24Google Scholar
  20. 20.
    Glenn JC (1946) Further studies on the effects of X-rays on phagocytic indeces of healthy rabbits. A preliminary report. J Immunol 53:95–100PubMedGoogle Scholar
  21. 21.
    Hallahan DE, Kuchibhotla J, Wyble C (1997) Sialyl Lewis X mimetics attenuate E-selectin-mediated adhesion of leukocytes to irradiated human endothelial cells. Radiat Res 147:41–47PubMedCrossRefGoogle Scholar
  22. 22.
    Hertveldt K, Philippe J, Thierens H et al (1997) Flow cytometry as a quantitative and sensitive method to evaluate low dose radiation induced apoptosis in vitro in human peripheral blood lymphocytes. Int J Radiat Biol 71:429–433PubMedCrossRefGoogle Scholar
  23. 23.
    Heyd R, Dorn AP, Herkströter M et al (2010) Radiation therapy for early stages of morbus Ledderhose. Strahlenther Onkol 186(1):24–29PubMedCrossRefGoogle Scholar
  24. 24.
    Hildebrandt G, Loppnow G, Jahns J et al (2003) Inhibition of the iNOS pathway in inflammatory macrophages by low-dose X-irradiation in vitro. Is there a time dependence? Strahlenther Onkol 179:158–166PubMedCrossRefGoogle Scholar
  25. 25.
    Hildebrandt G, Maggiorella L, Rodel F et al (2002) Mononuclear cell adhesion and cell adhesion molecule liberation after X-irradiation of activated endothelial cells in vitro. Int J Radiat Biol 78(4):315–325PubMedCrossRefGoogle Scholar
  26. 26.
    Hildebrandt G, Radlingmayr A, Rosenthal S et al (2003) Low-dose radiotherapy (LD-RT) and the modulation of iNOS expression in adjuvant-induced arthritis in rats. Int J Radiat Biol 79:993–1001PubMedCrossRefGoogle Scholar
  27. 27.
    Hildebrandt G, Seed MP, Freemantle CN et al (1998) Effects of low dose ionizing radiation on murine chronic granulomatous tissue. Strahlenther Onkol 174:580–588PubMedCrossRefGoogle Scholar
  28. 28.
    Howe GR, McLaughlin J (1996) Breast cancer mortality between 1950 and 1987 after exposure to fractionated moderate-dose-rate ionizing radiation in the Canadian fluoroscopy cohort study and a comparison with breast cancer mortality in the atomic bomb survivors study. Radiat Res 145:694–707PubMedCrossRefGoogle Scholar
  29. 29.
    Keilholz L, Seegenschmiedt MH, Kutzki D, Sauer R (1995) Periarthritis humeroscapularis (PHS). Indications, technique and outcome of radiotherapy. Strahlenther Onkol 171:379–384PubMedGoogle Scholar
  30. 30.
    Keilholz L, Seegenschmiedt H, Sauer R (1998) Radiotherapy for painful degenerative joint disorders. Indications, technique and clinical results. Strahlenther Onkol 174:243–250PubMedCrossRefGoogle Scholar
  31. 31.
    Kern PM, Keilholz L, Forster C et al (2000) Low-dose radiotherapy selectively reduces adhesion of peripheral blood mononuclear cells to endothelium in vitro. Radiother Oncol 54:273–282PubMedCrossRefGoogle Scholar
  32. 32.
    Kern P, Keilholz L, Forster C et al (1999) In vitro apoptosis in peripheral blood mononuclear cells induced by low-dose radiotherapy displays a discontinuous dose-dependence. Int J Radiat Biol 75:995–1003PubMedCrossRefGoogle Scholar
  33. 33.
    Leer JW, Houtte P van, Seegenschmiedt H (2007) Radiotherapy of non-malignant disorders: where do we stand? Radiother Oncol 83:175–177PubMedCrossRefGoogle Scholar
  34. 34.
    Liebmann A, Hindemith M, Jahns J et al (2004) Low-dose X-irradiation of adjuvant-induced arthritis in rats. Efficacy of different fractionation schedules. Strahlenther Onkol 180:165–172PubMedCrossRefGoogle Scholar
  35. 35.
    Lo TC (1999) Radiation therapy for heterotopic ossification. Semin Radiat Oncol 9:163–170PubMedCrossRefGoogle Scholar
  36. 36.
    Luckey TD (1980) Hormesis with Ionizing radiation. In: CRC Press, Boca RatonGoogle Scholar
  37. 37.
    Micke O, Seegenschmiedt MH (2004) Radiotherapy in painful heel spurs (plantar fasciitis)–results of a national patterns of care study. Int J Radiat Oncol Biol Phys 58:828–843PubMedCrossRefGoogle Scholar
  38. 38.
    Micke O, Seegenschmiedt MH (2002) Consensus guidelines for radiation therapy of benign diseases: a multicenter approach in Germany. Int J Radiat Oncol Biol Phys 52:496–513PubMedCrossRefGoogle Scholar
  39. 39.
    Mirzaie-Joniani H, Eriksson D, Sheikholvaezin A et al (2002) Apoptosis induced by low-dose and low-dose-rate radiation. Cancer 94:1210–1214PubMedCrossRefGoogle Scholar
  40. 40.
    Mucke R, Schonekaes K, Micke O et al (2003) Low-dose radiotherapy for painful heel spur. Retrospective study of 117 patients. Strahlenther Onkol 179:774–778PubMedCrossRefGoogle Scholar
  41. 41.
    Mücke R, Seegenschmiedt MH, Heyd R et al (2010) Radiotherapy in painful gonarthrosis. Results of a national patterns-of-care study. Strahlenther Onkol 186(1):7–17PubMedCrossRefGoogle Scholar
  42. 42.
    Muecke R, Micke O, Reichl B et al (2007) Demographic, clinical and treatment related predictors for event-free probability following low-dose radiotherapy for painful heel spurs—a retrospective multicenter study of 502 patients. Acta Oncol 46:239–246PubMedCrossRefGoogle Scholar
  43. 43.
    Nambi KS, Soman SD (1987) Environmental radiation and cancer in India. Health Phys 52:653–657PubMedCrossRefGoogle Scholar
  44. 44.
    Nguyen NP, Krafft SP, Vos P et al (2011) Feasibility of tomotherapy for Grave’s ophthalmopathy: Dosimetry comparison with conventional radiotherapy. Strahlenther Onkol 187(9):568–574PubMedCrossRefGoogle Scholar
  45. 45.
    Panés J, Granger DN (1998) Leukocyte-endothelial cell interactions: molecular mechanisms and implications in gastrointestinal disease. Gastroenterology 114:1066–1090PubMedCrossRefGoogle Scholar
  46. 46.
    Pierce DA, Preston DL (2000) Radiation-related cancer risks at low doses among atomic bomb survivors. Radiat Res 154:178–186PubMedCrossRefGoogle Scholar
  47. 47.
    Pokrajac B, Potter R, Wolfram RM et al (2005) Endovascular brachytherapy prevents restenosis after femoropopliteal angioplasty: results of the Vienna-3 randomised multicenter study. Radiother Oncol 74:3–9PubMedCrossRefGoogle Scholar
  48. 48.
    Prasad AV, Mohan N, Chandrasekar B, Meltz ML (1994) Activation of nuclear factor kappa B in human lymphoblastoid cells by low-dose ionizing radiation. Radiat Res 138:367–372PubMedCrossRefGoogle Scholar
  49. 49.
    Rodel F, Frey B, Capalbo G et al (2010) Discontinuous induction of X-linked inhibitor of apoptosis in EA.hy.926 endothelial cells is linked to NF-κB activation and mediates the anti-inflammatory properties of low-dose ionising-radiation. Radiother Oncol 97:346–351PubMedCrossRefGoogle Scholar
  50. 50.
    Rodel F, Hofmann D, Auer J et al (2008) The anti-inflammatory effect of low-dose radiation therapy involves a diminished CCL20 chemokine expression and granulocyte/endothelial cell adhesion. Strahlenther Onkol 184:41–47PubMedCrossRefGoogle Scholar
  51. 51.
    Rodel F, Kamprad F, Sauer R, Hildebrandt G (2002) Functional and molecular aspects of anti-inflammatory effects of low-dose radiotherapy. Strahlenther Onkol 178:1–9PubMedCrossRefGoogle Scholar
  52. 52.
    Rodel F, Keilholz L, Hermann M et al (2009) Activator protein 1 shows a biphasic induction and transcriptional activity after low dose X- irradiation in EA.hy.926 endothelial cells. Autoimmunity 42:343–345PubMedCrossRefGoogle Scholar
  53. 53.
    Roedel F, Kley N, Beuscher HU et al (2002) Anti-inflammatory effect of low-dose X-irradiation and the involvement of a TGF-beta1-induced down-regulation of leukocyte/endothelial cell adhesion. Int J Radiat Biol 78:711–719PubMedCrossRefGoogle Scholar
  54. 54.
    Rodel F, Schaller U, Schultze-Mosgau S et al (2004) The induction of TGF-beta(1) and NF-kappaB parallels a biphasic time course of leukocyte/endothelial cell adhesion following low-dose X-irradiation. Strahlenther Onkol 180:194–200PubMedCrossRefGoogle Scholar
  55. 55.
    Ruppert R, Seegenschmiedt MH, Sauer R (2004) Radiotherapy of osteoarthritis. Indication, technique and clinical results. Orthopade 33:56–62PubMedCrossRefGoogle Scholar
  56. 56.
    Sagan LA (1987) What is hormesis and why have not we heard about it before? Health Phys 52:521–525PubMedGoogle Scholar
  57. 57.
    Schaue D, Jahns J, Hildebrandt G, Trott KR (2005) Radiation treatment of acute inflammation in mice. Int J Radiat Biol 81:657–667PubMedCrossRefGoogle Scholar
  58. 58.
    Schaue D, Marples B, Trott KR (2002) The effects of low-dose X-irradiation on the oxidative burst in stimulated macrophages. Int J Radiat Biol 78:567–576PubMedCrossRefGoogle Scholar
  59. 59.
    Seegenschmiedt MH, Katalinic A, Makoski HB et al (1999) Radiotherapy of benign diseases: a pattern of care study in Germany. Strahlenther Onkol 175:541–547PubMedCrossRefGoogle Scholar
  60. 60.
    Seegenschmiedt MH, Keilholz L, Martus P et al (1997) Prevention of heterotopic ossification about the hip: final results of two randomized trials in 410 patients using either preoperative or postoperative radiation therapy. Int J Radiat Oncol Biol Phys 39:161–171PubMedCrossRefGoogle Scholar
  61. 61.
    Seegenschmiedt MH, Micke O, Willich N (2004) Radiation therapy for nonmalignant diseases in Germany. Current concepts and future perspectives. Strahlenther Onkol 180:718–730PubMedCrossRefGoogle Scholar
  62. 62.
    Stsjazhko VA, Tsyb AF, Tronko ND et al (1995) Childhood thyroid cancer since accident at Chernobyl. BMJ 310:801PubMedCrossRefGoogle Scholar
  63. 63.
    Trott KR (1994) Therapeutic effects of low radiation doses. Strahlenther Onkol 170:1–12PubMedGoogle Scholar
  64. 64.
    Trott KR, Parker R, Seed MP (1995) The effect of x-rays on experimental arthritis in the rat. Strahlenther Onkol 171:534–538PubMedGoogle Scholar
  65. 65.
    Tubiana M (2005) Dose-effect relationship and estimation of the carcinogenic effects of low doses of ionizing radiation: the joint report of the Academie des Sciences (Paris) and of the Academie Nationale de Medecine. Int J Radiat Oncol Biol Phys 63:317–319PubMedCrossRefGoogle Scholar
  66. 66.
    Tubiana M, Aurengo A, Averbeck D, Masse R (2006) The debate on the use of linear no threshold for assessing the effects of low doses. J Radiol Prot 26:317–324PubMedCrossRefGoogle Scholar
  67. 67.
    Von Pannewitz G (1970) Radiotherapy of arthrosis deformans. Method and results. Radiologe 10:51–54Google Scholar
  68. 68.
    Wolff S (1998) The adaptive response in radiobiology: evolving insights and implications. Environ Health Perspect 106(Suppl 1):277–283PubMedGoogle Scholar

Copyright information

© Urban & Vogel 2012

Authors and Affiliations

  • M. Arenas
    • 1
  • S. Sabater
    • 2
  • V. Hernández
    • 3
  • A. Rovirosa
    • 4
  • P.C. Lara
    • 5
  • A. Biete
    • 6
  • J. Panés
    • 7
  1. 1.Radiation Oncology Department. Hospital Universitari Sant Joan de Reus, Institut d’Investigacions Sanitàries Pere Virgili (IISPV)Universitat Rovira i Virgili (URV)ReusSpain
  2. 2.Radiation Oncology DepartmentComplejo Hospitalario Universitario de AlbaceteAlbaceteSpain
  3. 3.Physics DepartmentHospital Universitari Sant Joan de Reus, IISPVTarragonaSpain
  4. 4.Radiation Oncology DepartmentHospital Clínic de Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB)BarcelonaSpain
  5. 5.Radiation Oncology DepartmentHospital Universitario Dr Negrín, Las Palmas de Gran Canaria, Universidad Las Palmas de Gran Canaria (LPGC)CanariaSpain
  6. 6.Radiation Oncology DepartmentHospital Clínic de Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB)BarcelonaSpain
  7. 7.Gastroenterology DepartmentHospital Clínic de Barcelona, Institut de Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Universitat de Barcelona (UB)BarcelonaSpain

Personalised recommendations