Elevated Levels of Interleukin-18 are Associated with Lymph Node Metastasis in Papillary Thyroid Carcinoma

Abstract

Interleukin-18 (IL-18) is a proinflammatory cytokine that primarily stimulates the Th1 immune response. IL-18 exhibits anticancer activity and has been evaluated in clinical trials as a potential cancer treatment. However, evidence suggests that it may also facilitate the development and progression of some cancers. So far, the impact of IL-18 on papillary thyroid cancer (PTC) has not been investigated. In this study, we found that the expression of IL-18 was significantly increased in PTC compared to normal thyroid tissue. Elevated IL-18 expression was closely associated with lymphovascular invasion and lymph node metastases. Furthermore, compared to PTC patients with no nodal metastasis, serum IL-18 levels were slightly increased in patients with 1–4 nodal metastases and significantly elevated in patients with 5 or more nodal metastases. The pro-metastatic effect of IL-18 may be attributed to the simultaneous increase in the expression of S100A10, a known factor that is linked to nodal metastasis in PTC. In addition, the activation of several pathways, such as the intestinal immune network for lgA production and Staphylococcus aureus infection, may be involved in the metastasis process. Taken together, IL-18 may trigger pro-metastatic activity in PTC. Therefore, suppressing the function of IL-18 rather than enhancing it appears to be a reasonable strategy for treating aggressive PTC.