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Abstract Background Interleukin (IL)-22 plays important roles in the development of arterial disease, including atherosclerosis and hypertension. However, the relationship between IL-22 and acute thoracic aortic dissection (TAD) remains unknown. Methods Blood samples were collected from patients with chest pain who underwent computed tomography angiography of the thoracic aorta but had no known preoperative diagnosis of coronary artery disease, peripheral artery disease, arthritis, and/or membranous nephropathy. Patients were divided into non-AD (NAD) and TAD groups, and the plasma concentrations of IL-22, IL-6 and tumor necrosis factor (TNF)-α were measured. In addition, aortic tissue samples from acute TAD patients and normal donors were collected, and the expression levels of IL-22 and IL-22 receptor 1 (IL-22R1) were measured. Results IL-22, IL-6 and TNF-α levels were significantly higher in acute TAD patients than in NAD patients (IL-22, NAD group: 27.0 (19.1, 38.6) pg/ml vs. TAD group: 32.9 (20.6, 58.3) pg/ml, p < 0.0001). The correlation analysis showed that IL-22 levels were positively correlated with levels of IL-6, TNF-α, fasting glucose, blood pressure, white blood cells, C-reactive proteins and D-dimers. Binary logistic regression analyses showed that IL-22 was independently associated with the presence of acute TAD (OR 1.169, 95% CI 1.069 to 1.277; p = 0.001). In addition, compared with aortic tissue of normal controls, TAD aortas showed increased expression of IL-22 and IL-22R1, especially in the torn section (IL-22, non-torn section: 2.8 ± 0.5/HPF vs. torn section 2.8 ± 0.5/HPF, p < 0.001). Additionally, macrophage but not T lymphocyte infiltration was significantly increased in the torn section (Macrophage, non-torn section: 2.2 ± 0.6/HPF vs. torn section 5.7 ± 1.2/HPF, p < 0.001; T lymphocyte, non-torn section: 2.7 ± 0.9/HPF vs. torn section 2.4 ± 0.5/HPF, p = 0.28), as evidenced by increased positive staining for the macrophage marker CD68, as opposed to the T cell marker CD3. Conclusion IL-22 levels may correlate with the presence of acute TAD. Highlights • IL-22 expression was significantly increased both in the plasma and aortas of TAD. • IL-22 was independently associated with the presence of acute TAD and regulation of inflammation was the possible mechanism. • IL-22 may be a new biomarker for TAD and be useful for the diagnosis of TAD. [ABSTRACT FROM AUTHOR]