Increased burn-induced immunosuppression in lipopolysaccharide-resistant mice

Severe burns induce a state of immunosuppression, and the inflammatory response after burn injury may play a role in this phenomenon. This study examined the effect of the inflammatory response to endotoxin on burn-induced immunosuppression and oxidative stress. An endotoxin-resistant mouse strain (C3H/HeJ) and a normally responding mouse strain (C3H/HeN) were compared. The mice were separated into three groups of five animals for each experimental day: (1) saline, (2) buprenorphine, and (3) buprenorphine and 20% total body surface area burn. All animals were fed ad libitum. The inflammatory response was studied at 1, 4, 7, 10, and 14 days postburn. Proliferation of activated splenocytes in burn mice was significantly lower on days 7, 10, and 14 for the C3H/HeJ strain and on days 4 and 10 for the C3H/HeN strain. Globally, C3H/HeJ presented stronger immune suppression than C3H/HeN. Oxidative stress parameters (liver malonaldehyde, spleen metabolic activity, and thiol concentrations) were higher in endotoxin-resistant mice than in the control strain. Impairment of the inflammatory response was more pronounced and oxidative stress was greater in endotoxin-resistant burn mice than in normal burn controls. Buprenorphine administration was not related to depression of these immune parameters. The inflammatory response following burn injury may be beneficial to the immune system.     

Prophylactic treatment with fms-like tyrosine kinase-3 ligand after burn injury enhances global immune responses to infection

Severely burned patients are susceptible to infections with opportunistic organisms due to altered immune responses and frequent wound contamination. Immunomodulation to enhance systemic and local responses to wound infections may be protective after burn injury. We previously demonstrated that pretreatments with fms-like tyrosine kinase-3 (Flt3) ligand (Flt3L), a dendritic cell growth factor, increase the resistance of mice to a subsequent burn injury and wound infection by a dendritic cell-dependent mechanism. This study was designed to test the hypothesis that Flt3L administration after burn injury decreases susceptibility to wound infections by enhancing global immune cell activation. Mice were treated with Flt3L after burn injury and examined for survival, wound and systemic bacterial clearance, and immune cell activation after wound inoculation with Pseudomonas aeruginosa. To gain insight into the local effects of Flt3L at the burn wound, localization of Langerhans cells was examined. Mice treated with Flt3L had significantly greater numbers of CD25-expressing T cells and CD69-expressing T and B cells, neutrophils, and macrophages after, but not before, infection. Overall leukocyte apoptosis in response to infection was decreased with Flt3L treatment. Survival and local and systemic bacterial clearance were enhanced by Flt3L. Langerhans cells appeared in the dermis of skin bordering the burn wound, and further increased in response to wound infection. Flt3L augmented the appearance of Langerhans cells in response to both injury and infection. These data suggest that dendritic cell enhancement by Flt3L treatments after burn injury protects against opportunistic infections through promotion of local and systemic immune responses to infection.     

Acute burns

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the pathophysiology of burn injury. 2. Identify patient criteria for transfer to a burn center. 3. Calculate burn size and resuscitation requirements. 4. Treat inhalation injury in the acute setting. 5. Describe treatment options for burn injuries. 6. Describe preoperative selection, intraoperative procedures, and postoperative protocols for patients who require surgical care for their burn injuries. 7. Understand the survival and functional outcomes of burn injury. SUMMARY: The review article summarizes basic issues in the treatment of acute burn injury as practiced in 2008. The pathophysiology, treatment options, and expected outcomes for an acute burn are described and discussed. Special attention is directed to the nonoperative and surgical management of small to moderate-size burns that might be treated by the practicing plastic surgeon.     

Coping with severe burns in the early stage after burn injury

This study examined the relationship between coping strategies, anxiety and depression levels and burn injury characteristics in the early phase of the treatment in burn-injured patients. Seventy patients with severe burns were interviewed within two weeks of their burn trauma. Coping strategies were measured by the coping with burns questionnaire (CBQ). Anxiety and depression levels were assessed with the Beck Depression Inventory and the Beck Anxiety Inventory. There were no statistically significant gender differences in various coping strategies. Avoidance was associated with higher levels of anxiety, depression and hopelessness. The percentage of total body surface area (TBSA) and localization of burns were not associated with coping patterns. Implications for the assessment and management of burn injured patients were discussed.     

Burn injury initiates a shift in superantigen-induced T cell responses and host survival

Severe injury induces a temporal shift in immune reactivity that can cause serious complications or even death. We previously reported that mice exposed to bacterial superantigen (SAg) early after injury undergo a strong SAg response with lethal consequences. This study compares the early and late effects of burn injury on SAg reactivity in vivo to establish how injury influences adaptive immune responses. We found that mice challenged with ordinarily sublethal doses of staphylococcal enterotoxin A or staphylococcal enterotoxin B at 1 day after burn injury exhibited high mortality, whereas no mortality occurred at 7 days after injury. This shift in mortality correlated with higher Th2-type cytokines (IL-4 and IL-10) being expressed by CD4(+) and CD8(+) T cells from burn as opposed to sham mice at 7 days after injury. Lymph node cells from burn-injured mice also produced higher levels of Th2-type cytokines at 7 days after injury. The results of cell-mixing studies using CD4(+) and CD8(+) T cells mixed with APCs from sham or burn mice suggested that changes in both T cells and APCs are involved in the altered SAg response. Finally, the biological significance of altered SAg reactivity following injury was shown by demonstrating that blocking IL-10 activity in vivo caused higher SAg-induced mortality at 7 days after injury. These findings support the idea that injury promotes a Th2-type shift in adaptive immune reactivity. Although prior studies link this counterinflammatory-type response to lowered resistance to infection, the present results suggest it may sometimes benefit the injured host.     

重度烧伤患者细菌感染菌群分布及影响因素

目的 探讨重度烧伤患者细菌感染的菌群分布并分析其影响因素。 方法 选取我院2017年1月-2019年1月收治的重度烧伤患者212例,普通培养烧伤后10~15 d创面分泌物,观察细菌感染菌群分布情况,并从性别、年龄、烧伤深度、烧伤面积、低蛋白血症、糖尿病、早期休克、延迟复苏、血红蛋白尿、吸入性损伤、抗菌药物使用等方面分析重度烧伤患者感染的影响因素。 结果 212例重度烧伤患者中有89例患者发生创面感染,感染率为41.98％。89例发生创面细菌感染患者中:26例感染鲍氏不动杆菌,占29.21％;20例感染金黄色葡萄球菌,占22.47％;17例感染铜绿假单胞菌,占19.10％;12例感染肺炎克雷伯菌,占13.48％;8例感染大肠杆菌,占8.99％;4例感染变形杆菌,占4.49％;2例感染不动杆菌,占2.25％。影响重度烧伤患者细菌感染的单因素有烧伤面积、低蛋白血症、糖尿病、早期休克、延迟复苏、吸入性损伤(P结论 重度烧伤患者易发生细菌感染,感染影响因素有烧伤面积、低蛋白血症、糖尿病、早期休克、延迟复苏、吸入性损伤,临床应针对危险因素积极采取防治措施,控制细菌感染发生率,促进患者康复。     

Sex differences and estrogen modulation of the cellular immune response after injury

Cell-mediated immunity is extremely important for resolution of infection and for proper healing from injury. However, the cellular immune response is dysregulated following injuries such as burn and hemorrhage. Sex hormones are known to regulate immunity, and a well-documented dichotomy exists in the immune response to injury between the sexes. This disparity is caused by differences in immune cell activation, infiltration, and cytokine production during and after injury. Estrogen and testosterone can positively or negatively regulate the cellular immune response either by aiding in resolution or by compounding the morbidity and mortality. It is apparent that the hormonal dysregulation is dependent not only on the type of injury sustained but also the amount of circulating hormones. Therefore, it may be possible to design sex-specific therapies to improve immunological function and patient outcome.     

Oxidants and the pathophysiology of burn and smoke inhalation injury.

A skin burn is a common traumatic injury that results in both local tissue damage and a systemic mediator-induced response. There is evidence of both local and systemic oxidant changes manifested by lipid peroxidation in animal burn models and also in burned man. Both increased xanthine oxidase and neutrophil activation appear to be the oxidant sources. Animal studies have also demonstrated decreased burn edema, and also decreased distant organ dysfunction with the use of antioxidants, suggesting a cause-and-effect relationship, which needs to be tested in man. Smoke inhalation injury, a chemical injury to the airways caused by incomplete products of combustion, is frequently seen in conjunction with a body burn. Lipid peroxidation, both in lung and in distant organs, is also seen with this injury. The combined body burn and smoke inhalation injury lead to a marked increase in mortality rate and also an increase in the degree of generalized oxidant release and lipid peroxidation. Although data in man are limited, the available information, along with that from animal research on burns and smoke inhalation, indicates oxidants may well play a key role, and antioxidants may be of clinical therapeutic use.     

The isolated burned palm in children: epidemiology and long-term sequelae

The isolated burn of the palm is a typical injury in young children. Positioning and splinting in small hands is difficult, and long-term sequelae of these injuries are not uncommon. The objective of the present study was to assess the outcome of palm burns and to identify the risk factors for long-term sequelae. All patients admitted to our hospital affected with isolated palm injuries between January of 1988 and January of 1998 were reviewed. In total, 120 pediatric patients were admitted with isolated palm burns; 110 patients (91.7 percent) had partial-thickness burns, and 10 patients (8.3 percent) had full-thickness burns. Only four patients (3.3 percent) required excision and skin autografting, but all patients whose palms were operated on in the acute phase developed burn contractures. Sixteen patients (13.3 percent) developed palmar contractures, and more than half of them (56 percent) required reconstructive procedures. All palm burns that healed in more than 3 weeks developed scarring and sequelae (p<0.05 compared with no sequelae). Pediatric palmar burns are benign injuries with a low incidence of late sequelae. However, flame and contact burns are more prone to develop scarring. Excision and autografting should be performed on wounds that take over 3 weeks to heal, but it does not prevent late sequelae.     

Up-regulation of cell surface Toll-like receptors on circulating γδ T-cells following burn injury

Burn injury is associated with profound inflammation and activation of the innate immune system involving γδ T-cells. Similarly, Toll-like receptors (TLR) are associated with activation of the innate immune response; however, it is unclear whether TLR expression is altered in γδ T-cells after major burn injury. To study this, male C57BL/6 mice were subjected to burn injury (25% TBSA) and 1 or 7 days thereafter, blood and spleen cells were isolated and subjected to FACs analysis for TLRs and other phenotypic markers (γδ TCR, αβ TCR, CD69, CD120b). A marked increase in the number of circulating γδ T-cells was observed at 24 h post-burn (14% vs. 4%) and a higher percentage of these cells expressed TLR-2. TLR-4 expression was also increased post-burn, but to a lesser degree. These changes in TLR expression were not associated with altered CD69 or CD120b expression in γδ T-cells. The mobilization of, and increased TLR expression in, γδ T-cells was transient, as phenotypic changes were not evident at 7 days post-burn or in γδ T-cells from the circulation or spleen. The increases in TLR expression were not observed in αβ T-cells after burn injury. In conclusion, 24 h after burn injury mobilization of γδ T-cells with increased TLR expression was observed. This finding suggests that this unique T-cell population is critical in the innate immune response to injury, possibly through the recognition of danger signals by TLRs.     

Leukotoxin,a linoleate epoxide: Its implication in the late death of patients with extensive burns

Burn death based on circulatory shock is often encountered after recovery from primary shock in patients with deep and extensive burns,i.e., late death. Several toxic substances have been proposed, however, the responsible substance remains obscure. Since we have found leukotoxin, a highly cytotoxic linoleate epoxide biosynthesized by neutrophils, in the burned skin, in the present study we determined plasma leukotoxin concentrations in various degree of 30 burn patients. C-reactive protein and circulatory white blood cells were also measured. A significantly high mortality rate of patients with extensive burns (burn surface area over 70%) was observed compared with that in patients with burn surface area under 70%, and significantly high leukotoxin concentrations were observed within a week, and 3 weeks after the thermal injury in patients with extensive burns compared with those in patients with burn surface area under 70%. There were two peaks of plasma leukotoxin concentrations,i.e., the early phase (within 1 week) and the late phase (over 1 week) in patients with extensive burns. Plasma leukotoxin concentrations significantly correlated with burn surface area in the early phase, and similar correlations were observed in the late phase. A significantly high mortality rate (61%) of patients with peak leukotoxin concentrations over 30 nmol/ml was observed compared with 8% for those below 30 nmol/ml. Plasma leukotoxin concentration correlated significantly to C-reactive protein concentration, log (leukotoxin nmol/ml)=0.042×C-reactive protein (mg/dl)+0.74, (r=0.83,P<0.01) in the late phase. From these results, it is concluded that leukotoxin is produced in patients with burns particularly in the late phase of extensive burns, and leukotoxin might play an important role in the tissue destructive procedure associated with severe burns.     

Injury-induced suppression of effector T cell immunity requires CD1d-positive APCs and CD1d-restricted NKT cells

Overwhelming infection remains the leading cause of death from serious burn injury despite recent advances in the care of burn patients and a better understanding of immune and inflammatory consequences of injury. In this study, we report a critical requirement for CD1d-restricted NKT cells and CD1d expression by APCs in the immune dysfunction that occurs early after burn injury. Using a well-established murine scald injury model with BALB/c and BALB/c CD1d knockout mice, we investigated whether peripheral T cell immunity was affected by the presence or absence of CD1d-restricted NKT cells in the early stages after injury. Using Ag-specific delayed-type hypersensitivity, T cell proliferation, and cytokine production as indices of immune responsiveness, we observed that both CD1d expression by APCs and CD1d-restricted NKT cells are required for immune suppression after injury. Via adoptive transfer of splenocytes from injured mice to uninjured recipients, we found injury-induced suppression of immunity to be Ag specific, long lasting, and critically dependent on cell surface expression of CD1d by APCs. Together, our results suggest that the defects in T cell responsiveness that occur subsequent to severe burn injury are not merely the result of global or passive suppression, but instead represent an active form of CD1d/NKT cell-dependent immunologic tolerance.     

湖南省长株潭地区儿童烧伤流行病学调查研究

目的：总结分析湖南省长株潭地区儿童烧伤的流行病学特征。方法：采用分层随机抽样法抽取湖南省长株潭地区3所医院,收集其2010年1月至2010年12月间收治的0—14岁烧伤患儿病历资料,并对烧伤患儿或其家长进行问卷调查。、结果：各年龄段患儿烧伤构成比依次为0-3岁（62．1％）、4-6岁（24．2％）以及7—14岁（13．6％）。致伤原因构成比依次为热液烧伤（56．1％）、火焰烧伤（31．8％）、其他原因烧伤（12．1％）。83．3％的烧伤发生在室内,客厅为最主要的烧伤发生场所占47．3％。75．8％的患儿烧伤发生在白天（6：00-18：00）。62．5％的患儿烧伤发生在夏、秋两季（6月-11月）。结论：在长株潭地区,婴幼儿时期（0-3岁）为儿童烧伤的易发年龄段;热液／热蒸汽造成的烧烫伤是儿童烧伤最常见的类型;室内特别是客厅为儿童烧伤最容易发生的地点。白天和夏、秋两季为儿童烧伤的好发时段和季节。     

Puerarin alleviates burn-related procedural pain mediated by P2X3 receptors

Pain is a major problem after burns. Procedural pain evoked by burn dressing changes is common in patients, and its management is a critical part of treatment in acute burn injuries. Burn pain is very likely the most difficult form of acute pain to treat. ATP contributes to inflammation, and ATP is implicated in peripheral pain signaling via actions upon P2X₃ receptors. Puerarin is extracted from a traditional Chinese medicine and may act on P2X₃ receptor mechanisms. The Visual Analogue Scale (VAS) has been shown to be a sensitive indicator of pain intensity and treatment effects. Peripheral blood mononuclear cells (PBMCs) are involved in nociception or pain after burn injury. Burn patients were randomly divided into normal saline (NS) group (salt solution is saline) and puerarin-treated group and pain (Visual Analogue Scale scores) and inflammation (PBMCs) measured. Burn pain produces a stress response, so blood glucose, insulin, and cortisol levels in burn patients were determined. Furthermore, the expression of P2X₃ protein and mRNA in PBMCs was detected. The VAS scores in the puerarin-treated group were lower than those in NS group. The blood glucose, insulin, and cortisol levels in the puerarin-treated group at post-dressing changes were significantly decreased in comparison with those in NS group. The expression levels of P2X₃ protein and mRNA in PBMCs of burn patients in NS group were significantly increased in comparison with those in the puerarin-treated group. Puerarin can antagonize inflammatory factors (such as ATP) and decrease the upregulated expressions of P2X₃ protein and mRNA in PBMCs after burns to decrease VAS. Thus, puerarin had an analgesic effect on procedural pain in dressing changes of burn patients related to P2X₃ receptors.     

Arginine and ornithine kinetics in severely burned patients: increased rate of arginine disposal

Arginine serves multiple roles in the pathophysiological response to burn injury. Our previous studies in burn patients demonstrated a limited net rate of arginine de novo synthesis despite a significantly increased arginine turnover (flux), suggesting that this amino acid is a conditionally indispensable amino acid after major burns. This study used [15N2-guanidino-5,5-2H2]arginine and [5-13C]ornithine as tracers to assess the rate of arginine disposal via its conversion to and subsequent oxidation of ornithine; [5,5-2H2]proline and [5,5,5-2H3]leucine were also used to assess proline and protein kinetics. Nine severely burned patients were studied during a protein-free fast ("basal" or fast) and total parenteral nutrition (TPN) feedings. Compared with values from healthy volunteers, burn injury significantly increased 1) fluxes of arginine, ornithine, leucine, and proline; 2) arginine-to-ornithine conversion; 3) ornithine oxidation; and 4) arginine oxidation. TPN increased arginine-to-ornithine conversion and proportionally increased irreversible arginine oxidation. The elevated arginine oxidation, with limited net de novo synthesis from its immediate precursors, further implies that arginine is a conditionally indispensable amino acid in severely burned patients receiving TPN.     

Skeletal muscle apoptosis after burns is associated with activation of proapoptotic signals

Critical illness is associated with muscle wasting and muscle weakness. Using burn injury as a model of local and systemic inflammatory response, we tested the hypothesis that thermal injury causes apoptosis in muscle. After a 40% body surface area burn to rats, abdominal muscles beneath the burn and limb muscles distant from the burn were examined for apoptosis at varying times after burn. Ladder assay, ELISA, and histological methods showed evidence of apoptosis in the abdominal muscles within 4-12 h with peak changes occurring at 3-7 days. Maximal apoptosis was also evident at distant limb muscles at 3-7 days. Investigation of proapoptotic pathways indicated mitochondrial membrane potential to be altered by 1 h after burn. Starting at 15 min after burn, cytochrome c was released from the mitochondria into the cytosol, followed by increased activity of caspase-3, starting at 6 h after burn. These studies suggest that mitochondria and caspase-mediated apoptotic pathways may be an additional mechanism of muscle weight loss in burns and may be potential therapeutic targets for prevention of muscle wasting.     

IRAK contributes to burn-triggered myocardial contractile dysfunction

Major burn injury causes myocardial contractile dysfunction, but the molecular basis of this physiological response is incompletely understood. Previous studies demonstrated a role for the interleukin-1 receptor-associated kinase (IRAK) in the cardiac response to acute lipopolysaccharide administration as well as congestive heart failure. In this study, we examined the contribution of IRAK to burn-mediated cardiac responses. After burn injury, hearts from wild-type and IRAK-deficient mice were compared for intracellular signaling pathway activation and contractile function. IRAK-deficient hearts showed impaired activation of kinases that function downstream of IRAK and were partially protected against burn-induced contractile dysfunction. The findings demonstrate that IRAK and the Toll/interleukin-1 pathways participate in the response to large body surface area burns that leads to impaired cardiac contractility.