Association of IL-6 and IL-17 with thyroid eye disease

Background: Thyroid Eye Disease (TED) is the most common extrathyroidal manifestation of Graves' disease. Interleukin-6 (IL-6) and interleukin-17 (IL-17) have been implicated in its pathogenesis, but individual study results remain inconsistent. However, existing findings on IL-6 and IL-17 levels in the serum or tears of TED patients remain inconsistent. Aim: This meta-analysis aimed to statistically evaluate the level of IL-6 and IL-17 in patients with TED. Methods: A systematic literature search was conducted across five electronic databases (PubMed, Web of Science, Elsevier Science Direct, Wiley Online Library, and CNKI). The search strategy targeted the terms "Thyroid Eye Disease" in conjunction with "Interleukin-6" or "Interleukin-17" in title and abstract fields. Results are presented as standardized mean differences (SMD) with 95% confidence intervals (CI). Results: This meta-analysis demonstrated significantly elevated levels of both IL-6 and IL-17 in patients with TED compared to controls. Pooled estimates showed a substantial increase in IL-6 (SMD: 1.68; 95% CI: 0.83-2.53), with substantial heterogeneity. Similarly, IL-17 levels were markedly higher in TED patients overall (SMD: 1.78; 95% CI: 1.18-2.37). Furthermore, patients with active TED exhibited significantly higher IL-6 and IL-17 levels than those with inactive disease. Conclusions: To our knowledge, this meta-analysis is a large-scale systematic evaluation of IL-6 and IL-17 levels in patients with TED. These findings describe the circulating cytokine profile in the studied population and may inform future hypothesis-driven research. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261277844, identifier CRD420261277844.