Cytokines as new biomarkers of skin wound vitality

Background The diagnosis of skin wound vitality is currently based on standard histology, but histological findings lack sensitivity in case of a short survival time. New reliable biomarkers of vitality are therefore strongly needed. We assessed the ability of 10 candidate cytokines (IFN-gamma, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12p70, IL-13, TNF-alpha) to discriminate between vital and early post-mortem wounds. Methods Twenty-four cadavers with a recent open skin wound (< 3 h) were included (20 men, 4 women, mean age = 51.0 +/- 24.3 years). An early post-mortem wound was performed in an uninjured skin area, and both wounds were sampled at the autopsy (post-mortem interval (PMI) = 66.3 +/- 28.3 h). Needle-puncture sites related to resuscitation cares were included as very early post-mortem wounds (n = 6). In addition to standard histology, cytokines levels were simultaneously measured in each sample using a multiplex sandwich immunoassay, then normalized on healthy skin levels. A quantitative evaluation of IL-8-positive cells in ante- and post-mortem wound samples was also performed. Results In the training set of samples (n = 72), cytokine levels were significantly higher in vital wounds (mean age = 47 +/- 53 min) than in post-mortem wounds (mean PMI = 6.9 +/- 9.0 h) (p < 0.2), except for two cytokines (IFN-gamma and IL-2). IL-8 was the best discriminatory cytokine (Se = 54%, Sp = 100%, AUC = 0.79), while a multivariate model combining IL-4 and IL12p70 was a bit more discriminant (Se = 55%, Sp = 100%, AUC = 0.84). In the validation set (n = 72), the discriminatory power of the cytokines and the predictive model was slightly lower, with IL-8 remaining the best cytokine (Se = 46%, Sp = 96%, AUC = 0.75). The predictive model remained highly specific (Sp = 100%). Both the cytokines and the predictive model allowed the iatrogenic injuries to be correctly classified as post-mortem wounds. Standard histology and immunohistochemistry showed 21% sensitivity and a specificity of 79% and 100%, respectively. Only two iatrogenic wounds could be properly categorized histologically. Conclusion This study suggests that cytokines could be useful biomarkers of skin wound vitality and that the immunoassay method could be more sensitive than immunohistochemistry to identify wounds with a short survival time. Further research is underway to confirm these preliminary data.

Automated summary

This study evaluated the ability of 10 candidate cytokines to discriminate between vital and early post-mortem wounds, with IL-8 identified as the best discriminatory cytokine. Further research is needed to confirm these preliminary findings.