Differential expression of the immunoinflammatory response in trauma patients: Burn vs. non-burn☆
Introduction
Critical injuries, including severe head trauma and polytrauma, result in an elaboration of a wide range of inflammatory mediators, such as cytokines [1], [2]. Trauma can induce immune-inflammatory effects that are related to injury severity [3]. Severely injured patients have demonstrated early elevations in interleukin 6 (IL-6) and IL-8 [4], [5], [6], which have been associated with mortality [7], [8]. Giannoudis et al. found elevated IL-6 levels to be associated with a systemic inflammatory response syndrome (SIRS) state in which early elevations were predictive of complications such as pneumonia, multiple-organ dysfunction syndrome (MODS), and death in blunt trauma patients [9]. Likewise, Maier et al. found elevated IL-6 and soluble tumor necrosis factor (TNF) receptors to be predictive of mortality but IL-8 levels predictive of MODS in trauma patients [10].
In patients with burns, immune-inflammatory response is associated with complications after injury, such as infection, MODS, and mortality [11]. Burns have been associated with increased plasma TNF-α, IL-6, and IL-8 levels in comparison to elective surgery controls. Elevated levels of IL-6 and IL-8 were identified locally in burned skin [12]. In effect, IL-1β, IL-6, IL-8, and TNF-α levels have been correlated with total body surface area (TBSA) in burn patients [13], [14], [15], [16], [17], [18], [19]. In addition to soluble cellular adhesion molecules, elevated levels of TNF-α, IL-6, and IL-8 were associated with severe burns complicated by septic shock or death [14], [15], [20], [21], [22]. Although Drost et al. demonstrated an association among infection, IL-6, and TNF-α, IL-6 alone was associated with mortality in patients with burns [13], [23]. Unfortunately, not all studies are consistent. Gueugniaud et al., in a study of 10 patients with greater than 60% TBSA burned; found that survivors had higher IL-6 levels than non-survivors [24]. Recently, a study by Park et al. identified TNF-α as the only measured cytokine to predict mortality in burn and non-burn patient populations [25].
However, existing data still supports the notion that inflammatory cytokines play a role in the development of subsequent complications, including MODS. Cytokines are central mediators of the immunoinflammatory response to injury. Nonetheless, little is known about the specific roles that cytokines play in the response to injury and whether differences exist in the immunoinflammatory profiles between various patient populations. Specifically, we speculated that unique cytokine profiles exist for burn and non-burn trauma patients that are associated with outcome.
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Materials and methods
This study was conducted under a protocol reviewed and approved by the local institutional review board and in accordance with the approved protocol.
Results
During the study period, 179 hospitalized subjects and 20 healthy volunteers were enrolled and included in the analysis. Of the 179 subjects, 67 were admitted to the burn ICU and 112 to the surgical ICU with either blunt or penetrating traumatic injuries. Though the percentage of men and women between the groups was similar, subjects with burns were older with a lower ISS as an average for this population (Table 1). As a reflection of injury severity, subjects with burns had a high prevalence
Discussion
The period of recovery from a burn represents the extreme of hypermetabolism and catabolism possible in humans [1], [28]. It was expected patients with burns would have higher plasma cytokine levels than non-burn trauma patients; however, this study quantitatively demonstrates the significant difference in terms of plasma IL-6 and IL-8 levels. Burn was associated with a greater and more sustained immunoinflammatory response in terms of elevated IL-6 and IL-8 levels during the first week
Conclusions
In conclusion, burn patients had a greater and more sustained immune-inflammatory response, as reflected by plasma IL-6 and IL-8 levels, during the first week after injury than the non-burn trauma patients. The presence of MODS did not have a significant effect on plasma cytokine levels. Though we did not find associations between cytokine levels and outcome in this study, burn patients had a significantly worse outcome with higher mortality and more frequent multiple-organ dysfunction compared
Conflict of interest statement
None of the authors have any conflicts of interest or disclosures to report.
Acknowledgements
We acknowledge the laboratory support of the Department of Clinical Investigations by Kimberly Farrow, David Ho, Lisa Pérez, and Houston Kim in conducting the cytokine analyses and logistical support by Charlie Guymon. We also recognize the research nurses who supported this protocol, including Nancy Molter, Chaya Galin, Peggy Bielke, Kari Williams, Deb Deja, Elizabeth Frail, Juliette Castillo, and Michelle Morrow and the information technologists Nikolaos Kypreos and Jesús Morales, who
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The opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the views of the U.S. Department of the Army or the U.S. Department of Defense. This study was conducted under a protocol reviewed and approved by the U.S. Army Medical Research and Materiel Command Institutional Review Board and in accordance with the approved protocol.