131 Systemic Immune Response in Burn Patients studies have shown that trauma-induced immature neutrophils in blood of patients with systemic inflammation actually show decreased chemotactic activity and increased life-span, and therefore reside longer in the bloodstream then mature neutrophils [40– 42]. Also, it was shown that immature neutrophils have a reduced oxidative burst and phagocytic activity and that they are less potent in supporting innate immune defenses [42–44]. Another study showed that the reduced oxidative burst in neutrophils can last for up to 3.5 months [45]. It is however still unclear whether immature neutrophils are overall beneficial or detrimental for wound healing [46]. Nevertheless, our data demonstrate that burns can cause a long-lasting presence of both immature and mature neutrophils that may be harmful for wound healing, distant organs and survival. During wound healing, the first cells attracted to the site of injury are neutrophils, followed by monocytes, which upon arrival differentiate into macrophages or dendritic cells [47]. In response to acute systemic inflammation, the bone marrow releases its reserve of classical monocytes into the bloodstream to replace the monocytes that migrated into inflamed tissue [48]. CD14, a co-receptor of various Toll-like receptors, is increased on monocytes upon burn injury and helps to detect bacteria in the body [42,49]. We found increased numbers of all three monocyte subtypes in blood, while classical monocytes were the most prevalent. Classical monocytes mainly exert proinflammatory functions and can become monocyte-derived macrophages or dendritic cells upon infiltration of inflamed tissue [50]. Negative correlations were found between classical monocytes and MCP-1, a known chemoattractant for monocytes [51]. Binding of MCP-1 to CCR2 on circulating monocytes might have resulted in lower levels of free MCP-1 [52,53]. Alternatively, MCP-1 might have induced migration of classical monocytes toward affected tissues [52]. In this cohort of burn patients, the number of classical monocytes remained elevated for at least 39 days. Other studies on burn patients also found increased levels of classical monocytes during systemic inflammation [54]. Non-classical monocytes, that are described as more anti-inflammatory monocytes are thought to acquire the pro-healing macrophage phenotype (M2) in the injured tissue [52]. Although we found an increase in this monocyte subtype upon burn injury as well, their numbers were much lower than that of classical monocytes. Taken together, this might indicate that the balance of monocyte phenotypes is shifted toward a pro-inflammatory, rather than an anti-inflammatory state, that persists for weeks after burn injury. Later in the posttraumatic immune response (days to weeks), lymphocytes arrive at the site of injury to regulate the inflammation and support tissue restoration together with pro-healing macrophages [55]. To our knowledge there is no information on the dynamics of T cell activation and differentiation after burn injury in humans. Here, we established that while the number of lymphocytes in blood was largely unaffected upon burn injury, 4
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