Smoke inhalation enhances early alveolar leukocyte responsiveness to endotoxin
ABSTRACT Pulmonary dysfunction after smoke inhalation and thermal injury is associated with excessive morbidity and mortality. The purpose of this study was to evaluate alveolar leukocyte function after thermal injury and smoke inhalation.
Twenty-one patients with thermal injury only (n = 8); thermal injury and smoke inhalation injury (n = 8); and nonburned controls (n = 5) were assessed by means of bronchoscopically directed lavage (bronchoalveolar lavage [BAL]) on the first and fourth days postinjury. BAL-isolated pulmonary leukocytes were assessed for number, composition, viability, and production of tumor necrosis factor (TNF)alpha, interleukin (IL)-8, and IL-6 in response to 100 ng/mL of lipopolysaccharide (LPS) (mean +/- SEM; significance at p < 0.05).
Six of eight Smoke patients had gross evidence of lung injury. On day 1, Smoke and Burn BAL isolates yielded greater cell counts than Control (10.6 vs. 4.5 vs. 2.4 x 10(6)/mL). Smoke macrophages on day 1 produced more TNFalpha (1.2 vs. 0.2 ng/mL), IL-6 (8.0 vs. 1.9 ng/mL), and IL-8 (85 vs. 32 ng/mL) after LPS stimulation compared with respective unstimulated (0 ng/mL of LPS) day-1 Smoke cells. LPS-stimulated Burn cells on day 1 produced more IL-8 (150 vs. 62 ng/mL) but not TNFalpha (0.4 vs. 0.25 ng/mL) or IL-6 (1.8 vs. 0.69 ng/mL), when compared with respective unstimulated Burn cells. By day 4, LPS-stimulated Smoke and Burn cells produced significantly more TNFalpha (Smoke, 0.41 vs. 0.16 ng/mL; Burn, 0.87 vs. 0.51 ng/mL) and IL-6 (Smoke, 2.5 vs. 0.47 ng/mL; Burn, 4.1 vs. 1.47 ng/mL), but not IL-8 (Smoke, 51.1 vs. 51.1 ng/mL; Burn, 54.4 vs. 55.6 ng/mL), compared with respective unstimulated day-4 cells.
Smoke inhalation induces a massive influx of alveolar leukocytes that are primed for an early, enhanced LPS-activated cytokine response compared with alveolar leukocytes isolated after burn injury alone or normal controls.
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ABSTRACT: Acute lung injury (ALI) and its more severe form acute respiratory distress syndrome (ARDS) can result from both direct and indirect pulmonary damage caused by trauma and shock. In the course of ALI/ARDS, mediators released from resident cells, such as alveolar macrophages, may act as chemoattractants for invading cells and stimulate local cells to build up a pro-inflammatory micro-milieu. Depending on the trauma setting, the role of alveolar macrophages is differentially defined. This review focuses on alveolar macrophage function after blunt chest trauma, ischemia/reperfusion, hemorrhagic shock and thermal burns.Shock (Augusta, Ga.) 03/2014; 42(1). DOI:10.1097/SHK.0000000000000167 · 2.73 Impact Factor
Frontiers in Bioscience 01/2009; Volume(14):4618. DOI:10.2741/3554 · 4.25 Impact Factor
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ABSTRACT: The objective of this study was to evaluate the role of intraalveolar tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in a combination of skin burn and smoke inhalation injuries because this combined trauma is associated with an increased morbidity and mortality compared with either of these traumas alone. We used a standardized small animal model (rats n = 84) to investigate the early intraalveolar excretion of TNF-alpha during the first one, three, and six hours after a singular skin burn injury, singular smoke inhalation injury, and a combination involving both the traumas. The data were compared with the data from control rats that only received preparation and mechanical ventilation. The TNF-alpha serum levels and intraalveolar IL-6 concentrations were also measured. One hour after trauma, there was a significant difference in the TNF-alpha concentration between the controls and both the singular traumas (control vs burn P < .0444 and control vs smoke P < .005) and between the inhalation injury and the combined trauma (smoke vs burn + smoke P < .0084). After three and six hours, no significant differences among the groups were observed. Compared with the controls, both the singular skin burn and smoke inhalation injuries led to increased intraalveolar TNF-alpha excretion, whereas the combined trauma showed the least intraalveolar TNF-alpha levels at three and six hours post-trauma. These findings differed from the serum TNF-alpha levels. Compared with the IL-6 levels, we observed a negative correlation within the intraalveolar cytokine concentrations after one hour (r = -.809), three hours (r = -.627), and six hours (r = -.746). This study confirms the importance of the intraalveolar cytokine reaction in the early posttraumatic stage after a combined burn and inhalation injury. The differences between the combined and singular traumas indicate that TNF-alpha plays a role in the immunologic hyporesponsiveness of the lung and therefore in the systemic pathophysiological pathway, that often leads to patient mortality. In addition, an inverse correlation between TNF-alpha and IL-6, both classical markers of inflammation, in the intraalveolar space was observed.Journal of burn care & research: official publication of the American Burn Association 12/2014; 36(2). DOI:10.1097/BCR.0000000000000108 · 1.55 Impact Factor