Patrick Mulder

151 Local Immune Response in Burn Patients INTRODUCTION Burn injury is often accompanied by an extensive, derailed immune response in both burn wound tissue and peripheral blood [1,2]. Regardless of infection, burn patients generally show signs of systemic inflammation caused by high levels of cytokines and danger signals that originate from damaged tissue [3,4]. Necrotized and inflamed tissue stimulates the immune system to recruit acute phase immune cells to the affected site [2,5,6]. Fibroblasts and keratinocytes surrounding the wound site and infiltrating leukocytes release a storm of cytokines, chemokines and growth factors that initiate the inflammation phase [7]. Typically during wound healing, neutrophils and macrophages with a pro-inflammatory (i.e. M1) phenotype will migrate into the wounded skin to remove debris and prevent bacterial colonization [8]. Within days, wound neutrophils will disappear through apoptosis and macrophages will differentiate into a state that supports wound healing (i.e. M2 phenotype) [9]. Generally within one week after injury, lymphocytes will infiltrate the wound site to orchestrate tailored pathogen-eliminating and immune cell regulating responses [10]. The reduction, transition and control of immune cells are crucial for dampening of the inflammatory response and for the establishment of a healthy wound healing process. After burn injury however, the immune system can be overactive and is then likely to cause damage to surrounding tissues, delay wound healing and contribute to the severity of scarring [2,6]. Burn patients who experience persistent inflammation might benefit from immune suppressive treatment, however at the same time they are at risk of contracting infections such as pneumonia or cellulitis, caused by opportunistic bacteria [11]. Therefore, innovative and precise interventions that modulate the immune response could be crucial in the relief of secondary illnesses while improving wound healing and preventing infection. Still, there is only little information on the immune response after burn injury and how exactly it differs from normal wound healing, mainly due to its complexity and variation among cases (e.g. burn size, depth and cause) and burn patients (e.g. age, sex and co-morbidities) [12]. Moreover, present evidence on the processes that underlie burn injury originates mostly from animal research [13], which is only partially translatable to the human situation [14]. We previously showed that in blood from severely burned patients, there was an extreme increase in innate immune cells and pro-inflammatory cytokines [7]. In this longitudinal study, we investigated immune cells and soluble factors present in burn wound tissue (eschar) that was surgically debrided as part of standard treatment [15]. A better understanding of the immune reactions to burn injury will facilitate the design of improved and more targeted treatment approaches for trauma-induced immune dysfunction. 5

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