Cytokine production in patients with papillary thyroid cancer and associated autoimmune Hashimoto thyroiditis

Abstract

Hashimoto thyroiditis (HT) is the most frequent thyroid autoimmune disease, while papillary thyroid cancer (PTC) is one of the most common endocrine malignancies. A few patients with HT also develop PTC. The aim of this study was to analyze cytokine profiles in patients with PTC accompanied with autoimmune HT in comparison with those in patients with PTC alone or HT alone and healthy subjects. Cytokine levels were determined in supernatants obtained from phytohemagglutinin (PHA)-stimulated whole blood cultures in vitro. The concentrations of selected cytokines: Th1-interferon gamma (IFN-γ); Th2-interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 10 (IL-10) and interleukin 13 (IL-13); 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 found that PTC patients with HT produced significantly higher concentrations of IL-4, IL-6, IL-9, IL-13 and IFN-γ than PTC patients without HT. In conclusion, autoimmune HT affects the cytokine profile of patients with PTC by stimulating secretion of Th1/Th2/Th9 types of cytokines. Th1/Th2 cytokine ratios in PTC patients with associated autoimmune HT indicate a marked shift toward Th2 immunity.

Fig. 1

Mean concentrations of IL-4, IL-5, IL-13 and IL-9 secreted by PHA-stimulated whole blood cultures from healthy control subjects (HC, n = 12) and patients with Hashimoto thyroiditis (HT, n = 12) or papillary thyroid cancer (PTC, n = 12) or both papillary thyroid cancer and Hashimoto thyroiditis (PTC + HT, n = 4)

Fig. 2

Mean concentrations of IFN-γ, IL-6, IL-17A and IL-10 secreted by PHA-stimulated whole blood cultures from healthy control subjects (HC, n = 12) and patients with Hashimoto thyroiditis (HT, n = 12) or papillary thyroid cancer (PTC, n = 12) or both papillary thyroid cancer and Hashimoto thyroiditis (PTC + HT, n = 4)

Fig. 3

An overview of cytokine productions and Th1/Th2 cytokine ratios in PHA-stimulated blood cells from healthy controls, patients with Hashimoto thyroiditis (HT), patients with papillary thyroid cancer (PTC) and patients with papillary thyroid cancer and associated Hashimoto thyroiditis (PTC + HT). In patients with HT, the production of IFN-γ, IL-6 and IL-10 were increased, with marked shift toward Th1 immunity (Th1/Th2). In patients with PTC, the production of IL-13, IL-5 and IL-9 were increased, without a marked shift toward Th2 immunity (Th1/Th2). In patients with PTC + HT, the production of IL-13, IL-5, IL-9, IFN-γ and IL-6 were increased, with marked shift toward Th2 immunity (Th1/Th2)