Nuklearmedizin 2011; 50(05): 195-203
DOI: 10.3413/nukmed-04241108
Original article
Schattauer GmbH

Lymphocyte function following radioiodine therapy in patients with thyroid carcinoma

Lymphozytenfunktion nach Radioiodtherapie bei Patienten mit Schilddrüsenkarzinom
V. Barsegian
1   Department of Nuclear Medicine, Klinikum Dortmund
,
S. P. Müller
2   Department of Nuclear Medicine, University Hospital Essen
,
P. A. Horn
3   Institute for Transfusion Medicine, University Hospital Essen, Germany
,
A. Bockisch
2   Department of Nuclear Medicine, University Hospital Essen
,
M. Lindemann
3   Institute for Transfusion Medicine, University Hospital Essen, Germany
› Author Affiliations
Further Information

Publication History

received: 16 August 2011

accepted in revised form: 18 August 2011

Publication Date:
28 December 2017 (online)

Summary

Aim: Since the nuclear disaster in Fukushima has raised great concern about the danger of radioactivity, we here addressed the question if the therapeutic use of iodine 131, the most frequently applied radionuclide, was harmful to immune function in patients. It was our aim to define for the first time in a clinical setting how radioiodine therapy alters anti-microbial immune responses. Patients, methods: In 21 patients with thyroid carcinoma anti-microbial lymphocyte responses were assessed by lymphocyte transformation test and ELISpot – measuring lymphocyte proliferation and on a single cell level production of pro- and anti-inflammatory cytokines (interferon-γ and interleukin- 10) – prior to therapy, at day 1 and day 7 post therapy. Results: Proliferative lymphocyte responses and interferon-γ production after in vitro stimulation with microbial antigens were significantly (p < 0.05) increased at day 1 vs. pre therapy, and returned to pre therapy levels at day 7. On the contrary, at day 1 interleukin-10 production was significantly (p < 0.05) reduced. Thus, we observed a short-term increase in pro-inflammatory immune responses. However, T lymphocyte responses were in the range of healthy controls at all three time points. Conclusion: Thyroid carcinoma patients receiving radioiodine therapy do not display any sign of immunosuppression.

Zusammenfassung

Nachdem die nukleare Katastrophe in Fukushima zu großer Besorgnis wegen der Gefahren radioaktiver Strahlung geführt hat, stellten wir die Frage, ob die Therapie mit Iod-131, dem am häufigsten verwendeten Radionuklid, die Immunfunktion von Patienten beeinträchtigt. Es war unser Ziel, erstmals in einer klinischen Studie zu definieren, wie die Radioiodtherapie die Immunabwehr gegenüber Mikroorganismen beeinflusst. Patienten, Methoden: Bei 21 Patienten mit Schilddrüsenkarzinom wurde die Immunabwehr gegenüber Mikroorganismen mit dem Lymphozyten- Transformationstest und dem ELISpot – die entweder die Lymphozytenproliferation oder auf Einzelzell-Niveau die Bildung pround anti-inflammatorischer Zytokine (Interferon- γ und Interleukin-10) messen – vor der Therapie, an Tag 1 und Tag 7 nach der Therapie untersucht. Ergebnisse: Die Lymphozytenproliferation und die Interferon-γ-Produktion nach Stimulation mit mikrobiellen Antigenen waren an Tag 1 vs. vor Therapie signifikant (p < 0,05) höher. Die Reaktionen kehrten an Tag 7 auf das Ausgangsniveau zurück. Die Produktion von Interleukin-10 dagegen war an Tag 7 signifikant (p < 0,05) reduziert. Wir beobachteten also kurzzeitig einen Anstieg proinflammatorischer Immunantworten. Allerdings waren die Reaktionen der T-Lymphozyten zu allen drei Zeitpunkten im Normbereich. Schlussfolgerung: Bei Patienten mit Schilddrüsen karzinom, die eine Radioiodtherapie erhalten, findet sich kein Hinweis auf eine Immun suppression.

 
  • References

  • 1 Anderson RE, Lefkovits I. Effects of irradiation on the in vitro immune response. Exp Cell Biol 1980; 48: 255-278.
  • 2 Anderson RE, Warner NL. Ionizing radiation and the immune response. Adv Immunol 1976; 24: 215-335.
  • 3 Apostoloff E, Friedel E, Apostoloff G. et al. Cellular immunological reactions in vivo and vitro in higher age. ZFA 1980; 35: 211-213.
  • 4 Belka C, Ottinger H, Kreuzfelder E. et al. Impact of localized radiotherapy on blood immune cells counts and function in humans. Radiother Oncol 1999; 50: 199-204.
  • 5 Choi KM, Kang CM, Cho ES. et al. Ionizing radiation-induced micronucleus formation is mediated by reactive oxygen species that are produced in a manner dependent on mitochondria, Nox1, and JNK. Oncol Rep 2007; 17: 1183-1188.
  • 6 Dehos G, Hinz G, Schwarz E-R. Changes in number and function of the lymphocyte populations as a biological indicator for ionizing radiation. Kaul A, Dehos A, Bögl W. et al. Biological indicators for radiation dose assessment.. München: MMV; 1986: 298-301.
  • 7 Federico G, Boni G, Fabiani B. et al. No evidence of chromosome damage in children and adolescents with differentiated thyroid carcinoma after receiving 131I radiometabolic therapy, as evaluated by micronucleus assay and microarray analysis. Eur J Nucl Med Mol Imaging 2008; 35: 2113-2121.
  • 8 Furhang EE, Larson SM, Buranapong P. et al. Thyroid cancer dosimetry using clearance fitting. J Nucl Med 1999; 40: 131-136.
  • 9 Galdiero M, Cipollaro de, l'Ero G, Folgore A. et al. Effects of irradiation doses on alterations in cytokine release by monocytes and lymphocytes. J Med 1994; 25: 23-40.
  • 10 Gradzka I, Iwanenko T. A non-radioactive, PFGE-based assay for low levels of DNA double-strand breaks in mammalian cells. DNA Repair (Amst) 2005; 4: 1129-1139.
  • 11 Grosse-Wilde H, Schaefer UW. Radiopathology of Organs and Tissues: Lymphatic System. Scherer E, Streffer C, Trott K-R. Medical Radiology.. Berlin, Heidelberg: Springer; 1991: 171-190.
  • 12 Guedeney G, Grunwald D, Malarbet JL. et al. Time dependence of chromosomal aberrations induced in human and monkey lymphocytes by acute and fractionated exposure to 60Co. Radiat Res 1988; 116: 254-262.
  • 13 James SE, Arlett CF, Green MH. et al. Radiosensitivity of human T-lymphocytes proliferating in long term culture. Int J Radiat Biol Relat Stud Phys Chem Med 1983; 44: 417-422.
  • 14 Joseph LJ, Bhartiya US, Raut YS. et al. Micronuclei frequency in peripheral blood lymphocytes of thyroid cancer patients after radioiodine therapy and its relationship with metastasis. Mutat Res 2009; 675: 35-40.
  • 15 Lassmann M, Hanscheid H, Chiesa C. et al. EANM Dosimetry Committee series on standard operational procedures for pre-therapeutic dosimetry I: blood and bone marrow dosimetry in differentiated thyroid cancer therapy. Eur J Nucl Med Mol Imaging 2008; 35: 1405-1412.
  • 16 Lassmann M, Hanscheid H, Gassen D. et al. In vivo formation of gamma-H2AX and 53BP1 DNA repair foci in blood cells after radioiodine therapy of differentiated thyroid cancer. J Nucl Med 2010; 51: 1318-1325.
  • 17 Lindemann M, Barsegian V, Runde V. et al. Transfer of humoral and cellular hepatitis B immunity by allogeneic hematopoietic cell transplantation. Transplantation 2003; 75: 833-838.
  • 18 Lindemann M, Barsegian V, Siffert W. et al. Role of G protein beta3 subunit C825T and HLA class II polymorphisms in the immune response after HBV vaccination. Virology 2002; 297: 245-252.
  • 19 Lindemann M, Böhmer J, Zabel M. et al. ELISpot: a new tool for the detection of nickel sensitization. Clin Exp Allergy 2003; 33: 992-998.
  • 20 Lindemann M, Schuett P, Moritz T. et al. Cellular in vitro immune function in multiple myeloma patients after high-dose chemotherapy and autologous peripheral stem cell transplantation. Leukemia 2005; 19: 490-492.
  • 21 Lindemann M, Virchow S, Ramann F. et al. The G protein beta3 subunit 825T allele is a genetic marker for enhanced T cell response. FEBS Lett 2001; 495: 82-86.
  • 22 MacKenzie D. Fukushima radioactive fallout nears Chernobyl levels. New Scientist 2011. cited 2011 August 10 www.webcitation.org/5xRjHTuh3
  • 23 Mutschler J, Steinbach G, Bunjes D. et al. Myeloablative radioimmunotherapy with 188Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-alpha. Nuklearmedizin 2009; 48: 30-36.
  • 24 Publication 53, Radiation dose to patients from radiopharmaceuticals. Annals of the ICRP.. Oxford: Pergamon Press; 1987: 31-375.
  • 25 Schrek R, Stefani S. Resistance of phytohaemagglutinin-treated lymphocytes to X-rays and nitrogen mustard. Nature 1963; 200: 482-483.
  • 26 Ugurel S, Lindemann M, Schadendorf D. et al. Altered surface expression patterns of circulating monocytes in cancer patients: impaired capacity of T-cell stimulation?. Cancer Immunol Immunother 2004; 53: 1051.
  • 27 Watanabe N, Kanegane H, Kinuya S. et al. The radiotoxicity of 131I therapy of thyroid cancer: assessment by micronucleus assay of B lymphocytes. J Nucl Med 2004; 45: 608-611.