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Necrotizing fasciitis (NF) has emerged as rare but rapidly progressive, life-threatening severe skin and soft tissue infection. We conducted a study to investigate whether Th1/Th2 cytokines could serve as biomarkers to distinguish NF from class III skin and soft tissue infections (SSTIs). A retrospective review was performed for 155 patients suffering from serious skin and soft tissue infections from October 2020 to February 2022. Th1/Th2 cytokines were obtained from peripheral blood and wound drainage fluid samples. Data on demographic characteristics, causative microbiological organisms, Th1/Th2 cytokines, c-reactive protein, procalcitonin and white blood cell (WBC) were extracted for analysis. Factors with statistical difference(p < 0.1) were included in the multivariate logistic regression model. The clinical differential diagnostic values of interleukin-2(IL-2), IL-6, IL-10, tumor necrosis factor-α (TNF-α) and interferon-r (IFN-r) were analyzed by receiver operating characteristic (ROC) curve. Among the 155 patients, 66(43%) patients were diagnosed as NF. We found no significant difference for sex, age, location of infection, coexisting condition, predisposition, duration of symptoms before admission and micro-organisms, WBC, procalcitonin and c-reactive protein in NF and class III SSTIs group. NF had higher levels of IL-6 in serum (50.46 [24.89, 108.89] vs. 11.87 [5.20, 25.32] pg/ml; p＜0.01), IL-10 in serum (3.45 [2.03, 5.12] vs. 2.51 [1.79, 3.29] pg/ml; p＜0.01), IL-2 in wound drainage fluid (0.89 [0.49, 1.33] vs. 0.63 [0.14, 1.14] pg/ml; p = 0.02), IL-6 in wound drainage fluid (5000.84 [1392.30, 13287.19] vs. 1927.82 (336.65, 6759.27) pg/ml; p＜0.01), TNF-a in wound drainage fluid (5.20 [1.49, 22.97] vs. 0.96 [0.12, 3.21] pg/ml; p＜0.01) and IFN-r in wound drainage fluid (1.32 [0.47, 4.62] vs. 0.68 [0.10, 1.88] pg/ml; p = 0.02) as compared to the class III SSTIs. Multivariate logistic regression analyses showed that IL-6 in serum, IL-10 in serum and TNF-a in wound drainage fluid exhibited independently significant associations with diagnosis of NF(p＜0.05). In ROC curve analysis of IL-2, IL-6, IL-10, TNF-a and IFN-r for diagnosis of NF, the area under the curve (AUC) of IL-6 in serum could reach to 0.80 (p＜0.001). Using 27.62 pg/ml as the cut off value, the sensitivity was 74% and the specificity was 79% in IL-6 in serum. Th1/Th2 cytokines, IL-6 in serum in particular, are potential biomarkers for the diagnosis of NF in the early stage. However, larger patient populations with multiple centers and prospective studies are necessary to ensure the prognostic role of Th1/Th2 cytokines. • Th1/Th2 cytokines could be a potential diagnostic tool for NF in the early stage. • IL-6 in serum had the best diagnostic value for NF. • Larger patient populations and prospective studies are necessary to ensure the prognostic role of Th1/Th2 cytokines. [ABSTRACT FROM AUTHOR]