Toll-like receptor responses are suppressed in trauma ICU patients.

BACKGROUND: Inflammation and activation of the innate immune system are often associated with traumatic injury and may involve alterations in toll-like receptor (TLR)-mediated responses. METHODS: A prospective observational study was designed and conducted. Twenty-one severely injured (ISS = 16-41) trauma intensive care unit (ICU) patients and six healthy volunteers that served as controls were enrolled. Anticoagulated whole blood was collected at 2-12 d after ICU admission and incubated in the presence of media alone (baseline), zymosan (TLR2 agonist) or lipopolysaccharide (LPS; TLR4 agonist) for 3 h. Supernatant levels of inflammatory cytokines (IL-1ß, IL-6, IL-10, and TNFα) were determined. RESULTS: TLR2-mediated and TLR4-mediated activation of whole blood cell cultures from both healthy volunteers and subjects-induced elevated cytokine levels over that observed in unstimulated cultures. Baseline values of IL-6 were significantly elevated in subject cultures as compared to healthy volunteers. Healthy volunteer cultures had 2-3-fold greater levels of IL-6 and TNFα than subject cultures when stimulated with zymosan (TLR2 agonist) or LPS (TLR4 agonist). IL-1ß and IL-10 levels did not differ significantly between healthy volunteers and subjects. CONCLUSIONS: The ability of circulating leukocytes from trauma ICU patients to be activated by TLR agonists is markedly suppressed and may play a role in the development of subsequent infectious complications.

The association between the Th-17 immune response and pulmonary complications in a trauma ICU population.

BACKGROUND: The overall immunopathology of the T-helper cell (Th)-17 immune response has been implicated in various inflammatory diseases including pulmonary inflammation; however its potential role in acute respiratory distress syndrome (ARDS) is not defined. This study aimed to evaluate the Th-17 response in bronchoalveolar lavage fluid (BALF) and blood and from trauma patients with pulmonary complications. METHODS: A total of 21 severely injured intensive care unit (ICU) subjects, who were mechanically ventilated and undergoing bronchoscopy, were enrolled. BALF and blood were collected and analyzed for Th-1 (interferon [IFN]γ), Th-2 (interleukin [IL]-4, -10), Th-17 (IL-17A, -17F, -22, 23) and pro-inflammatory (IL-1ß, IL-6, tumor necrosis factor [TNF]α) cytokine levels. RESULTS: Significant levels of the Th-17 cytokines IL-17A, -17F and -21 and IL-6 (which can be classified as a Th-17 cytokine) were observed in the BALF of all subjects. There were no significant differences in Th-17 cytokines between those subjects with ARDS and those without, with the exception of plasma and BALF IL-6, which was markedly greater in ARDS subjects, as compared with controls and non-ARDS subjects. CONCLUSIONS: Trauma patients with pulmonary complications exhibited a significant Th-17 response in the lung and blood, suggesting that this pro-inflammatory milieu may be a contributing factor to such complications.

Dermal γδ T-Cells Can Be Activated by Mitochondrial Damage-Associated Molecular Patterns.

BACKGROUND: Gamma delta T-cells have been shown to be important to the early immunoinflammatory response to injury, independent of infection. This unique T-cell population acts to regulate cell trafficking and the release of cytokines and growth factors. We propose this sterile inflammatory response is in part associated with damage associated molecular patterns (DAMPs) generated by major injury, such as burn, and mediated via toll-like receptors (TLRs). It is unknown whether DAMPs can activate resident γδ T-cells that reside in skin. METHODS: Gamma delta T-cells were isolated from the skin of male C57BL/6 mice by enzymatic digestion. Mitochondrial DAMPs (MTDs) were generated from mitochondria isolated from mouse livers by sonication and centrifugation. Dermal γδ T-cells were incubated with MTDs (0-500 µg/ml) for 24 hr and cells and supernatants were collected for analysis. RESULTS: MTDs activated dermal γδ T-cells, as evidenced by increased TLR2 and TLR4 expression following in vitro exposure. MTDs also induced the production of inflammatory cytokines (IL-1ß, IL-6), and growth factors (PDGF and VEGF) by γδ T-cells. CONCLUSIONS: These findings herein support the concept that MTDs released after tissue/cellular injury are capable of activating dermal γδ T-cells. We propose that the activation of this unique T-cell population is central in the initiation of sterile inflammation and also contributes to the subsequent healing processes.

Small Bowel Perforations by Metallic Grill Brush Bristles: Clinical Presentations and Opportunity for Prevention.

Increasing reports on the incidental ingestion of metallic bristles from barbeque grill cleaning brushes have been reported. We sought to describe the clinical presentation and grilling habits of patients presenting after ingesting metallic bristles in an attempt to identify risk factors. We performed a chart review of six patients with documented enteric injury from metallic bristles. Subjects were contacted and administered a survey focused on the events surrounding the bristle ingestion. We arranged for in-home visits to inspect the grill and grill brush whenever possible. Of the six subjects identified, three (50%) were male, five (83%) were white, and they ranged in age from 18 to 65 years (mean 42.5). All complained of abdominal pain. All bristles were identified by CT scan. Three patients underwent laparoscopic enterorrhaphy, and two underwent laparotomy. The remaining patients did not require intervention. None had replaced their grill brush in at least two years. Surgeon's awareness of this unusual injury is important to identify and manage this problem. Alternative methods to clean the grill should be sought and grill brushes should be replaced at least every two years.

The contribution of opiate analgesics to the development of infectious complications in trauma patients.

Trauma-related pain is a natural consequence of injury and its surgical management; however, the relationship between opiates and complications in trauma patients is unknown. To study this a retrospective chart review of selected subjects following traumatic injury with admission to the SICU for > 3 days was performed, and opiate administration data was collected for the first 3 days of admission. Associated data from each subject's chart was also collected. Analysis of the data revealed that increased opiate intake after admission to the SICU was associated with significantly increased SICU and hospital LOS independent of injury severity. This increase in LOS was independent of mechanical ventilation in the moderate ISS group. Infectious complications were also more prevalent in the moderate ISS group with higher opiate use. These findings suggest that increased doses of opiate analgesics in trauma patients may contribute to an increased overall LOS and associated infectious complications. Analgesic regimes that minimize opiate intake, while still providing adequate pain relief, may be advantageous in reducing LOS, complications and reduce hospitalization costs.

The Th-17 response and its potential role in post-injury pulmonary complications.

Trauma is a leading cause of death and morbidity among all ages and constitutes a major public health problem. This burden is initially directed at stabilizing direct injury, however, post-trauma complications are common and prolong costly ICU stays. Among these complications are acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). While care for these pulmonary complications has now been standardized and prevention continues to improve, the true pathophysiology has not been elucidated. Current evidence suggests that the activation of a pro-inflammatory cascade plays an important role in the pathogenesis of trauma related lung injury. Additionally, there is a novel T-cell response that has been shown to be intricately involved in other non-traumatic lung diseases and multiple inflammatory diseases. With the recent discovery of this novel T-helper subset (Th-17) and the main effector cytokine, IL-17, there is the potential for further categorizing the biologic mechanism leading to ALI and ARDS. By utilizing the discoveries provided by animal models and further investigation into local and systemic cytokine profiles in human trauma victims, the information gained holds promise in the development of unique therapeutic modalities for the treatment and prevention of ARDS following traumatic injury.