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Cytokine production in peripheral blood cells of patients with differentiated thyroid cancer: elevated Th2/Th9 cytokine production before and reduced Th2 cytokine production after radioactive iodine therapy

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Abstract

Cytokines play a key role in the regulation of cells of the immune system and also have been implicated in the pathogenesis of malignant diseases. The aim of this study was to evaluate cytokine profiles in patients with differentiated thyroid cancer (DTC) before and 7 days after radioactive iodine (131-I) therapy. Cytokine levels were determined in supernatants obtained from phytohemagglutinin-stimulated whole blood cultures of 13 patients with DTC and 13 control subjects. The concentrations of selected cytokines: Th1—interferon gamma (IFN-γ), interleukin 2 (IL-2) and tumor necrosis factor alpha (TNF-α); Th2—interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 13 (IL-13) and interleukin 10 (IL-10); Th9—interleukin-9 (IL-9); and Th17—interleukin 17 (IL-17A) were measured using multiplex cytokine detection systems for Human Th1/Th2/Th9/Th17/Th22. We have shown that peripheral blood cells of DTC patients produce significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. The 131-I therapy led to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Despite this, the calculated cytokine ratios (Th1/Th2) in DTC patients before and 7 days after 131-I therapy were not different from those in healthy subjects. DTC patients have significantly higher concentrations of Th2/Th9 cytokines (IL-5, IL-13 and IL-9) than control subjects. There is no influence of hypothyroidism or stage of disease on cytokine production in DTC patients before 131-I therapy. The radioactive 131-I therapy leads to reduced secretion of Th2 cytokines (IL-4, IL-5 and IL-13). Additional studies are needed to determine the significance of these findings.

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Abbreviations

131-I:

Iodine 131

DTC:

Differentiated thyroid cancer

EANM:

European Association of Nuclear Medicine

IFN-γ:

Interferon gamma

IL-2:

Interleukin 2

IL-4:

Interleukin 4

IL-5:

Interleukin 5

IL-9:

Interleukin 9

IL-10:

Interleukin 10

IL-13:

Interleukin 13

IL-17A:

Interleukin 17A

PHA:

Phytohemagglutinin

SD:

Standard deviation

Th1:

T-helper-1

Th2:

T-helper-2

Th9:

T-helper-9

Th17:

T-helper-17

TNF-α:

Tumor necrosis factor alpha

TSH:

Thyroid-stimulating hormone

TxN0M0:

Patients without any proven metastases

TxNxM0:

Patients with nodal metastases

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Acknowledgments

The study was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (Grant Nos. III41010 and ON175069).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Faculty of Medical Sciences, University of Kragujevac, Svetozara Markovica 69, 34000, Kragujevac, Serbia

    Snezana Zivancevic Simonovic, Olgica Mihaljevic, Predrag Djurdjevic, Irena Kostic, Olivera Milosevic Djordjevic & Ljiljana Mijatovic Teodorovic

  2. Institute for Medical Research, Military Medical Academy, Belgrade, Serbia

    Ivana Majstorovic

  3. Department of Nuclear Medicine, Clinical Center Kragujevac, Kragujevac, Serbia

    Ljiljana Mijatovic Teodorovic

Authors
  1. Snezana Zivancevic Simonovic
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  2. Olgica Mihaljevic
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Correspondence to Snezana Zivancevic Simonovic.

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Simonovic, S.Z., Mihaljevic, O., Majstorovic, I. et al. Cytokine production in peripheral blood cells of patients with differentiated thyroid cancer: elevated Th2/Th9 cytokine production before and reduced Th2 cytokine production after radioactive iodine therapy. Cancer Immunol Immunother 64, 75–82 (2015). https://doi.org/10.1007/s00262-014-1619-7

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  • DOI: https://doi.org/10.1007/s00262-014-1619-7

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