18 Chapter 1 AIM AND THESIS OUTLINE To limit secondary complications and thereby improve patients’ overall health and outcome, it is paramount to improve our understanding of the pathophysiological reactions to burn injury. The research aim of this thesis was to improve our understanding of the burn-induced immune response and to develop an in vitro skin model to study cellular reactions without the need for animal experimentation. This thesis is divided into four parts that describe the pursuit of this aim step by step. In Part 1, the empirical evidence regarding burn-induced immune response in animal models is systematically reviewed. Two systematic reviews were performed that synthesize the available literature on the levels of immune cells (Chapter 2) and inflammatory factors (Chapter 3) after burn injury. Meta-analyses and subgroups analyses were performed to reveal time-depend effects and to identify factors of influence. Part 2 of this thesis is focused on the immune response in burn patients. These data were generated using blood and post-operative burn tissue samples from patients. The systemic and local immune profile after burn injury in time was studied by analyzing immune cells and cytokines using flow cytometry and immunohistochemistry. For comparison, blood and skin from healthy subjects were used. Chapter 4 describes the dynamics and phenotypic changes of immune cells and response levels of effector molecules in patient blood. In Chapter 5 the effect of burn injury on immune cells and inflammatory mediators in burn wound tissue is displayed. Part 3 of this thesis contains the experimental work with full skin equivalent models to simulate aspects of burn injury in vitro. Chapter 6 shows the optimization and validation of our full skin equivalent model that can be used to study burn wound healing and the concomitant cytokine response. In Chapter 7 the full skin equivalent model was supplemented with T cells or monocyte-derived macrophages to study their phenotype and reactions within this model of burn injury. The findings in this thesis are put into a broader perspective in Chapter 8, Chapter 9 and Chapter 10, which contain the General Discussion, English Summary and Dutch Summary (Nederlandse Samenvatting).
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