Reduction of plasma granzyme A correlates with severity of sepsis in burn patients.

The risk of mortality is high in burn patients and correlates with age, burn area extent, and sepsis. Immunosuppression has been reported to occur after severe burn. Cytotoxic cells possess specialized granules containing perforin and a group of serine proteases (granzymes). Granzyme A is a serine protease constitutively expressed by gammadelta and NK cells, in agreement with their functional cytolytic potential. In vitro studies have shown that GrA may be released extracellularly during cytotoxic cell degranulation, indicating the activation of cytotoxic cells. The aim of our study was to determine plasma GrA activity in burned patients and to verify if decreased GrA levels were associated with poor prognosis. Specific GrA activity was tested in the plasma of burned and healthy subjects by esterase assay. Plasma GrA was significantly decreased in septic rather than in nonseptic burn patients and in healthy subjects (p < 0.05 and p < 0.001, respectively). At day 3 plasma GrA was significantly lower in nonsurvivor than in survivor septic patients (p < 0.05). The value of 91 mOD showed a sensitivity of 100% and a specificity of 84% in differentiating survivor from nonsurvivor septic patients. Because this is a retrospective study, Granzyme A is not a confirmed predictor of septic outcome after burn, but its determination could give useful information about the development and severity of sepsis.

Circulating dendritic cells following burn.

Burns are associated with immune suppression and subsequent development of sepsis. Dendritic cells (DCs) are potent antigen-presenting cells that serve as a critical link between the innate and acquired immune systems, and are essential in coordinating the host response to pathogens. Using multicolour flow cytometry, the percentages of LIN(-) DR(+) CD11c(+) myeloid (mDC) and LIN(-) DR(+) CD123(+) plasmacytoid (pDC) subsets were determined in peripheral blood from 32 people (15 septic and 5 non-septic burn victims and 12 age- and gender-matched healthy controls, up to 20 days from injury). Analysis revealed significant reductions in circulating mDCs and pDCs in survivor as well as non-survivor septic cases compared with non-septic cases and controls (p<0.001). These findings suggest that deficiencies in mDCs and pDC subsets are related to sepsis following severe burn, and may contribute to immunosuppression among burn victims.

Skin dendritic cells in burn patients.

The body's immunological response to burn injury has been a subject of great inquiry in recent years. Burn injury disturbs the immune system, resulting in a progressive suppression of the immune response that is thought to contribute to the development of sepsis. Dendritic cells (DCs) are potent antigen-presenting cells that possess the ability to stimulate naïve T cells.DCs are derived from bone marrow progenitors and circulate in the blood as immature precursors prior to migration into peripheral tissues. Within different tissues, DCs differentiate and become active in the taking up and processing of antigens, and their subsequent presentation on the cell surface is linked to major histocompatibility molecules. Upon appropriate stimulation, DCs undergo further maturation and migrate to secondary lymphoid tissues, where they present antigen to T cells and induce an immune response. The purpose of this study was to determine the effects of burn injury on skin DCs in terms of percentage, HLA-DR, and Toll-like receptor-4 (TLR-4) expression. The skin DCs were isolated from burned skin and non-burned skin in the same patient at 7 days post-injury, and skin DCs were isolated from unburned healthy individuals as control. DCs from burned skin notably express low levels of HLA-DR and TLR-4 soon after cell isolation. In the post-burn period the ability of skin DCs to respond to bacterial stimuli is impaired. These changes in DC behaviour might contribute to the impaired host defences against bacteria during burn sepsis.

Concentrations of cytokines IL-6 and IL-10 in plasma of burn patients: their relationship to sepsis and outcome.

Burn injury induces a suppression of the Th1 response, which is associated with an increased susceptibility to conditions of infection, morbidity, and mortality. It is well established that cytokines modulate the pathogenesis of burn injury. In this study, plasma levels of interleukin-6 (IL-6) and interleukin-10 (IL-10) were determined in burn patients and correlated with the severity of sepsis. Sixty adult burn patients (total body surface area burned, 8-80%) were included in the study, of whom 34 developed sepsis and 14 died. The nonseptic group consisted of 26 patients. Thirty-one healthy blood donors served as controls. Patients were not treated with antibiotics until sepsis occurred. Plasma samples were collected immediately post-burn and after several days, and cytokine concentrations were determined by ELISA. Within three days, all the patients presented high levels of circulating IL-6, which were significantly higher in septic patients than in nonseptic patients (349 ± 278 vs 63 ± 56 pg/ml, p < 0.001).IL-10 levels were higher in septic patients than in nonseptic patients at all times in our study. The value of 60 pg/ml shows a sensitivity of 92% and a specificity of 93% in the differentiation of survivor from nonsurvivor septic patients. In this study the high value of circulating IL-10 on day 3 suggests that cytokine may discriminate between nonsurvivor septic and survivor septic patients.

Decrease of circulating dendritic cells in burn patients.

Burn injury is associated with immune suppression and the subsequent development of sepsis. Severe burn injury is associated with depressed immune response, including a functional impairment of Th1 lymphocytes and natural killer cells and a decrease in interferon-a production. Dendritic cells (DCs) are potent antigen-presenting cells and play a key role in T cell activation; they are essential in coordinating the host response to pathogens. Using three-colour flow cytometry, we determined the percentage of lineage-negative LIN-DR+ DCs in burn patients and healthy subjects. The percentages of DCs were lower in the circulation of septic than in nonseptic patients and healthy subjects at all times examined (14 days) after burn injury. In contrast, the DC percentage in nonseptic patients was low at day 1, increased from day 3 to day 10, and reverted to normal levels at day 14. The data from the present study suggest that the DC percentage decreased early after burn injury. In addition, in the presence of severe sepsis, the DC percentage remained lower until day 14. This DC reduction may contribute to the immunosuppression observed after burn injury.

[Psychosocial intervention model of neonatal intensive care in Modena]. / Il modello di intervento psicosociale della Terapia Intensiva Neonatale di Modena.

Many authors agree that psychosocial factors influence the psychophysical development of the infant. These factors must be taken into account in the neonatal care. At the neonatal intensive care unit (NICU) of the University Hospital of Modena, physicians, psychologist and nurses cooperate to take care of each newborn with a difficult psychosocial background. Together they individuate and select newborns with psychosocial difficulties, plan an integrated action and, eventually, address the family to the community services. We describe our experience with 106 cases from 1996 to 1999. The integrated action included observation of parental behavior within the NICU and psychological support for parents by means of psychological counselling. Many meetings among physicians, nurses, psychologist and the social worker were needed to achieve good results. The aim of the project was to define a method to provide individualized actions in order to favour psychophysical health of newborns and their families.