119 Systemic Immune Response in Burn Patients INTRODUCTION Burn injury and its consequences affect patients’ overall health and quality of life because of long-term functional and cosmetic impairment [1]. Severe burn trauma induces pro-inflammatory immune responses in peripheral blood and affected tissues, regardless of infection [2,3]. This immune response can persist up to months and can lead to additional health problems, including systemic inflammatory response syndrome (SIRS), hypermetabolic state and damage to surrounding tissues and even distant organs [4–7]. Trauma instantly causes inflammation and produces damage associated molecular patterns (DAMPs) through necrotic and injured tissue, which stimulates the immune system to recruit acute phase immune cells [8,9]. A well-orchestrated immune response is essential for a proper healing process, as a persistent and dysregulated immune reaction can negatively affect wound closure and tissue repair. For example, an overactive immune system can cause tissue damage by proteases and oxygen radicals released by innate immune cells, and by hypercoagulation-induced ischemia [10,11]. Such collateral damage can even be linked to excessive scarring [12], which in turn cause debilitating deficiencies affecting physical, psychological and social aspects. So far, studies examining burn-induced systemic inflammation centered on data obtained from animal models [13]. The human response to trauma is however quite distinct from that of animals, which is exemplified by differences in wound healing and scar formation [14]. Data on the mechanisms behind the propagation and regulation of burn-induced immune response in humans is still very limited [15]. After initiation of the acute phase immune response due to burn injury, neutrophils and macrophages are the first immune cells homing to the wound area [1]. Neutrophils and macrophages originate from the blood circulation and are replenished by the bone marrow. These innate immune cells remove necrotic tissue and defend the body from pathogens by phagocytosis and the release of reactive oxygen species [16]. In this inflammatory phase, the innate immune cells enhance the inflammation and recruit other immune cells by secreting soluble mediators [3]. In the late phase of inflammation, T cells, originating from lymphoid tissues, and anti-inflammatory macrophages resolve the inflammation to limit ancillary damage to the tissue [17]. In trauma, T cell subtypes Th1 and Th17 cells play a role in the enhancement of inflammation, whereas Th2 and regulatory T cells (Tregs) are involved in its resolution [18]. A balance between these subtypes is essential for a proper transition from inflammation to wound healing [19]. In a normal wound healing situation, i.e. after minor injuries, neutrophils disappear from the wound area through apoptosis and macrophages differentiate from a proinflammatory state to a tissue remodeling state to re-establish homeostasis and initiate the proliferation phase wherein restoration of the skin can take place [20]. 4
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