Extracellular ATP dysregulation leads to chronic wounds via the IL-6/NLRP3/ROS axis in patients

Chronic wounds are an expensive public health problem that greatly impacts society. The lack of pathophysiological understating impairs the proper management and treatment of this disease. In this study, we aimed to search for the sociodemographic characteristics, biochemical markers, immunological and redox profiles, as well as purinergic signaling in patients with chronic wounds. In addition, we performed a statistical analysis to predict wound chronification by the peripheral biomarkers. Sociodemographically, patients with chronic wounds were predominantly caucasian males. We found that patients had increased levels of c-protein reactive and blood glucose, and reduction in albumin. The immunological profile analysis showed elevated levels of IL-6. The redox profile confirmed that patients presented an increase in ROS, accompanied by a reduction in levels of PSH and enzymatic activity of SOD. About purinergic signaling, we discovered increased levels of eATP and alterations in the purinergic cascade in PBMCS and platelets. An overexpression of CD39 and NLRP3 was found. Finally, levels of ROS, PSH, IL-6, and eATP were indicated as good predictors of wound chronification. For the first time, we discovered that elevated rates of extracellular ATP are responsible for chronic inflammation and oxidative stress in the chronification process of wounds with deleterious impacts on healing. Monitoring the levels of highlighted peripheral biomarkers may significantly contribute to the treatment of wounds by mitigating the chronification of lesions. We suggest that our findings may apply to clinical outcomes in the treatment of chronic wounds.