Abstract
Background: Interleukin-6 (IL-6) is a key inflammatory cytokine implicated in atherosclerotic plaque progression and carotid vulnerability. Although elevated IL-6 levels have been linked to cerebrovascular risk, its prognostic value in patients undergoing carotid endarterectomy (CEA) remains undefined. This systematic review aimed to investigate the available evidence on the relationship between IL-6 levels, surgical outcomes and mechanistic evidence in CEA patients. Materials and Methods: The review followed the PRISMA statement and AMSTAR-2 critical appraisal guidelines, with the protocol registered on PROSPERO (CRD420251120023). PubMed/MEDLINE, Scopus, and Web of Science were systematically searched up to July 2025 using the terms "interleukin-6" and "carotid endarterectomy". Original studies in humans assessing IL-6 in relation to clinical outcomes after CEA or mechanistic evidence were included without language or date restrictions. Study quality was evaluated using the Cochrane Risk of Bias 2 and NHLBI tools, and evidence certainty was appraised using the GRADE framework. Given the heterogeneity of studies, only a qualitative synthesis was performed. Results: From 1232 records identified, 13 studies encompassing 1396 patients met the inclusion criteria. Most were prospective observational cohorts, with a mean participant age of 68.52 years and 81.16% male predominance. Perioperative stroke and mortality rates were uniformly low (≤2%), consistent with contemporary registry data. Across studies, elevated IL-6 levels-whether systemic or plaque-derived-were consistently associated with symptomatic carotid disease, plaque vulnerability, and adverse long-term outcomes. However, not all studies presented quantitative data on IL-6 levels, limiting the ability to draw definitive prognostic conclusions. Conclusions: Current evidence supports a mechanistic link between IL-6-mediated inflammation and carotid plaque instability, yet robust clinical validation in surgical populations is lacking. Future large-scale, prospective studies incorporating IL-6 measurement are warranted to establish its prognostic utility, guide anti-inflammatory therapeutic strategies, and refine postoperative risk stratification in patients undergoing CEA.