Modelling and modulation of the inflammatory response in severe burns

Patients with major burns experience a profound hypermetabolic inflammatory response which not only affects the skin but also has systemic effects in other organs. Although trauma and sepsis both result in a state of hypermetabolism, the degree in burns is substantially higher. As a result there is a pressing need for novel strategies to diminish and regulate this response. At present no treatment for this condition exists, and no prognostic model is available to support clinical decision making and personalized treatment. This project included studying an innovative treatment, Alkaline Phosphatase, in critical care burn patients, and the development of a mathematical model that allows us to understand and simulate the dynamics of the inflammatory response after burns. In a phase I study, we treated 10 severely burned patients, 7 men and 3 women, with Alkaline Phosphatase for 7 days. Burn size varied between 16% and 38% of the body surface area. The clinical outcomes and levels of inflammatory markers of these patients are compared with that of 20 conventionally treated patients. The developed mathematical model includes various integrated cell biological components and several key factors were identified to influence the inflammatory response in the first four days post burn, such as the initial number of endothelial cells. The data from the phase 1 study is used to validate the model. The results of this project will be used to further unravel the burn wound healing process, allow the development new treatment strategies, and optimise intensive care decision processes towards individual patient specific treatment.