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Increased serum interleukin-37 (IL-37) levels correlate with oxidative stress parameters in Hashimoto’s thyroiditis

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Abstract

Purpose

Interleukin-37 (IL-37), member of the IL-1 family, is a natural suppressor of immune and inflammatory responses. Increased serum IL-37 levels were observed in several autoimmune diseases, including Graves’ disease. To our knowledge, no data on Hashimoto’s thyroiditis (HT) are available in the literature.

Methods

Aim of our study was to measure serum IL-37 levels and evaluate their relationship, if any, with oxidative stress markers in HT patients. We enrolled 45 euthyroid HT patients (5 M e 40 F, median age 40 years) and 50 age- and sex-matched healthy controls. None was under l-thyroxine therapy. Serum IL-37 levels were measured by ELISA. Specific serum tests, such as derived reactive oxygen metabolites (d-ROMs), and biological anti-oxidant potential (BAP) test were performed in all subjects to investigate the changes in oxidative balance, and advanced glycation end products (AGEs) were determined as a specific marker of oxidative stress.

Results

IL-37 levels were significantly higher in HT than in controls (median 475 vs. 268 pg/ml, P = 0.018). In the same patients, serum oxidants (d-ROMs) were increased and anti-oxidants (BAP) decreased compared with controls (P = 0.011 and < 0.0001, respectively), clearly indicating an enhanced oxidative stress. In addition, AGEs levels were higher in HT patients than in controls (210 vs. 140 AU/g prot, P < 0.0001) and directly correlated with IL-37 levels (P = 0.048). At multivariate analysis, the main independent predictors that influenced IL-37 levels were both anti-thyroid antibodies (P = 0.026) and AGEs levels (P = 0.001).

Conclusions

IL-37 is up-regulated in HT and may exert a protective role by counteracting oxidative stress and inflammation.

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Funding

This work was not supported by any grant.

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Authors and Affiliations

  1. Unit of Endocrinology, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    R. M. Ruggeri, T. M. Vicchio & S. Giovinazzo

  2. Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy

    M. Cristani & A. Saija

  3. Unit of Statistical and Mathematical Sciences, Department of Economics, University of Messina, Messina, Italy

    A. Alibrandi

  4. Unit of Nuclear Medicine, Department of Biomedical and Dental Sciences, and Morpho-Functional Images, University of Messina, Messina, Italy

    A. Campennì

  5. Accademia Peloritana dei Pericolanti, University of Messina, Messina, Italy

    F. Trimarchi

  6. Department of Clinical and Experimental Medicine, Postgraduate School and Division of Allergy and Clinical Immunology, University of Messina, Messina, Italy

    S. Gangemi

  7. UOC di Endocrinologia, Dipartimento di Medicina Clinica e Sperimentale, Padiglione H, 4 piano - Policlinico Universitario “G. Martino”, 98125, Messina, Italy

    R. M. Ruggeri

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Each author gave a substantial contribute to the paper and approved the final version to be published.

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Correspondence to R. M. Ruggeri.

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The study was performed in comply with ethical standards which is in accordance with the 1964 Helsinki Declaration and its later amendments. This article does not contain any studies with animals performed by any of the authors.

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Ruggeri, R.M., Cristani, M., Vicchio, T.M. et al. Increased serum interleukin-37 (IL-37) levels correlate with oxidative stress parameters in Hashimoto’s thyroiditis. J Endocrinol Invest 42, 199–205 (2019). https://doi.org/10.1007/s40618-018-0903-3

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