Exposure to DBP and High Iodine Aggravates Autoimmune Thyroid Disease Through Increasing the Levels of IL-17 and Thyroid-Binding Globulin in Wistar Rats

Toxicol Sci. 2018 May 1;163(1):196-205. doi: 10.1093/toxsci/kfy019.


Autoimmune thyroid disease (AITD) is the most common autoimmune disease that causes hypothyroidism. High iodine is a well-known factor that can induce thyroid disorders, including Hashimoto's thyroiditis, one of the main types of AITD. Recent epidemiological studies have indicated that phthalates, especially di-n-butyl phthalate (DBP) may induce thyroid disease. In this study, we aim to determine the effects and underlying mechanisms of high iodine and/or DBP exposure on AITD. Female Wistar rats were modeled with thyroglobulin and exposed to high iodine and/or DBP. We investigated histopathological changes in the thyroid and measured thyroid hormone levels in serum to assess thyroid function. In the thyroid and liver, we detected oxidative stress, proinflammatory factors (IL-1β, IL-6, and IL-17) and the activation of activator protein 1 (AP-1), a transcription factor that is related to the synthesis of the thyroxine-binding globulin (TBG) and the activation of Th17. After blocking AP-1 with SP600125, we detected TBG and the Th17 related cytokines (IL-6 and IL-17). The data showed that thyroid damage and the alteration of thyroid hormones were greater when the rats were exposed to both high iodine and DBP. Coexposure to DBP and high iodine enhanced the activation of AP-1 in the liver and thyroid, and induced an increase in the levels of TBG in serum and IL-17 in the thyroid. Blocking AP-1 activation prevented the increase of TBG and IL-17. The results indicate that high iodine and/or DBP exposure exacerbated AITD through altering TBG levels in serum and aggravating IL-17 in the thyroid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / blood
  • Autoimmune Diseases / chemically induced*
  • Autoimmune Diseases / immunology
  • Dibutyl Phthalate / toxicity*
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Female
  • Interleukin-17 / metabolism*
  • Iodine / toxicity*
  • Liver / drug effects
  • Liver / metabolism
  • Oxidative Stress / drug effects
  • Oxidative Stress / immunology
  • Rats, Wistar
  • Thyroid Diseases / blood
  • Thyroid Diseases / chemically induced*
  • Thyroid Diseases / immunology
  • Thyroid Gland / drug effects
  • Thyroid Gland / immunology
  • Thyroid Gland / pathology
  • Thyroid Hormones / blood
  • Thyroxine-Binding Globulin / metabolism*


  • Interleukin-17
  • Thyroid Hormones
  • Thyroxine-Binding Globulin
  • Dibutyl Phthalate
  • Iodine