Publications (3)12.32 Total impact
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ABSTRACT: Chest trauma frequently occurs in severely injured patients and is often associated with hemorrhagic shock. Immune dysfunction contributes to the adverse outcome of multiple injuries. The aims of this study were to establish a combined model of lung contusion and hemorrhage and to evaluate the cardiopulmonary and immunologic response. Male mice were subjected to sham procedure, chest trauma, hemorrhage (35 mm Hg±5 mm Hg, 60 minutes), or the combination. Respiratory rate, heart rate, and blood pressure were monitored. Plasma, Kupffer cells, blood monocytes, splenocytes, and splenic macrophages were isolated after 20 hours. Tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, 10, 12, 18, and macrophage inflammatory protein-2 levels in plasma and culture supernatants were determined. Heart rate and blood pressure dropped in all groups, and after chest trauma and the double hit, these values remained reduced until the end of observation. Blood pressure was lower after the double hit than after the single hits. Plasma and Kupffer cell TNF-α concentrations were increased after lung contusion but not further enhanced by subsequent hemorrhage. Peripheral blood mononuclear cell (PBMC) TNF-α and IL-6 release were suppressed after the combined insult. IL-18 concentrations were increased in PBMC supernatants after chest trauma and in splenic macrophage supernatants of all groups. Although physiologic readouts were selectively altered in response to the single or double hits, the combination did not uniformly augment the changes in inflammation. Our results suggest that the leading insult regarding the immunologic response is lung contusion, supporting the concept that lung contusion represents an important prognostic factor in multiple injuries.
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ABSTRACT: Blunt chest trauma is accompanied by an early increase in plasma cytokine concentrations. However, the local sources of these mediators are poorly defined. We investigated the impact of blunt chest trauma on the inflammatory mediator milieu in different compartments (lung tissue, bronchoalveolar lavage, liver tissue, Kupffer cells, plasma) along with the time course of trauma-induced pulmonary endothelial barrier dysfunction to elucidate potential relationships. In addition, the correlation between intratracheally instilled interleukin-6 and its systemic release were studied. Prospective, randomized, controlled animal study. Basic science laboratory of a university affiliated level 1 trauma center. Male C3H/HeN mice, 8-9 wks old, n = 141. Blunt chest trauma induced by a focused blast wave, intravenous injection of Evans blue, and intratracheal instillation of recombinant human interleukin-6. Two hours after blunt chest trauma, plasma interleukin-6 was markedly increased. Simultaneously, interleukin-6, tumor necrosis factor-alpha, macrophage inflammatory protein-2, monocyte chemotactic polypeptide-1 and neutrophil/monocyte accumulation in bronchoalveolar lavage and interleukin-6, monocyte chemotactic polypeptide-1, and myeloperoxidase activity in lung tissue were significantly increased. This was accompanied by a coinciding elevation in the Evans blue lung-plasma ratio. Recombinant human interleukin-6, instilled intratracheally before blunt chest trauma, was detected in a dose-dependent manner in the plasma of the mice. Additionally, Kupffer cell interleukin-6, tumor necrosis factor-alpha, and interleukin-10 production was significantly augmented as early as 30 mins after the insult. These results indicate that early increased cytokine concentrations in the lung, particularly interleukin-6, are important mediator sources as their local peak coincides with the systemic inflammatory response and is accompanied by a simultaneous impaired function of the pulmonary endothelial barrier. A direct relationship between their local and systemic concentrations can be established. Furthermore, this is the first study to show that Kupffer cells are activated early after blunt chest trauma.
Ulm, Baden-Württemberg, Germany
- Clinic of Trauma, Hand, Plastic and Reconstructive Surgery