Transcompartmental Inflammatory Responses in Humans: IV Versus Endobronchial Administration of Endotoxin
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Transcompartmental Inflammatory Responses in Humans : IV Versus Endobronchial Administration of Endotoxin. / Plovsing, Ronni R; Berg, Ronan M G; Evans, Kevin A; Konge, Lars; Iversen, Martin; Garred, Peter; Møller, Kirsten.
I: Critical Care Medicine, Bind 42, Nr. 7, 07.2014, s. 1658–1665.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Transcompartmental Inflammatory Responses in Humans
T2 - IV Versus Endobronchial Administration of Endotoxin
AU - Plovsing, Ronni R
AU - Berg, Ronan M G
AU - Evans, Kevin A
AU - Konge, Lars
AU - Iversen, Martin
AU - Garred, Peter
AU - Møller, Kirsten
PY - 2014/7
Y1 - 2014/7
N2 - OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysaccharide-induced pulmonary and systemic inflammation.DESIGN: Randomized, double-blind, placebo-controlled, crossover study.SETTING ICU SUBJECTS: Healthy male volunteers.INTERVENTIONS: Fifteen volunteers (mean age, 23; SD, 2 yr) received Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV or endobronchially on two different study days. Groups were evaluated by bronchoalveolar lavage at baseline (0 hr) and 2, 4, 6, 8, or 24 hours postchallenge. Cardiorespiratory variables were continuously recorded throughout the study day, and plasma and bronchoalveolar lavage fluid markers of inflammation were measured.MEASUREMENTS AND MAIN RESULTS: IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p < 0.001). Furthermore, a delayed (6-8 hr) increase in bronchoalveolar lavage fluid interleukin-6 concentration (p < 0.001) and alveolar leukocyte count (p = 0.03) and a minor increase in bronchoalveolar lavage fluid tumor necrosis factor-α were observed (p = 0.06). Endobronchial endotoxin was followed by progressive alveolar neutrocytosis and increased bronchoalveolar lavage fluid tumor necrosis factor-α, interleukin-6, and albumin (all p < 0.001); a systemic inflammatory response was observed after 2-4 hours, with no change in plasma tumor necrosis factor-α.CONCLUSIONS: Acute lung or systemic inflammation in humans is followed by a transcompartmental proinflammatory response, the degree and differential kinetics of which suggests that the propagation of inflammation may depend on the primary site of injury.
AB - OBJECTIVES: Transcompartmental signaling during early inflammation may lead to propagation of disease to other organs. The time course and the mechanisms involved are still poorly understood. We aimed at comparing acute transcompartmental inflammatory responses in humans following lipopolysaccharide-induced pulmonary and systemic inflammation.DESIGN: Randomized, double-blind, placebo-controlled, crossover study.SETTING ICU SUBJECTS: Healthy male volunteers.INTERVENTIONS: Fifteen volunteers (mean age, 23; SD, 2 yr) received Escherichia coli endotoxin (lipopolysaccharide, 4 ng/kg) IV or endobronchially on two different study days. Groups were evaluated by bronchoalveolar lavage at baseline (0 hr) and 2, 4, 6, 8, or 24 hours postchallenge. Cardiorespiratory variables were continuously recorded throughout the study day, and plasma and bronchoalveolar lavage fluid markers of inflammation were measured.MEASUREMENTS AND MAIN RESULTS: IV endotoxin elicited a systemic inflammatory response with a time-dependent increase and peak in tumor necrosis factor-α, interleukin-6, and leukocyte counts (all p < 0.001). Furthermore, a delayed (6-8 hr) increase in bronchoalveolar lavage fluid interleukin-6 concentration (p < 0.001) and alveolar leukocyte count (p = 0.03) and a minor increase in bronchoalveolar lavage fluid tumor necrosis factor-α were observed (p = 0.06). Endobronchial endotoxin was followed by progressive alveolar neutrocytosis and increased bronchoalveolar lavage fluid tumor necrosis factor-α, interleukin-6, and albumin (all p < 0.001); a systemic inflammatory response was observed after 2-4 hours, with no change in plasma tumor necrosis factor-α.CONCLUSIONS: Acute lung or systemic inflammation in humans is followed by a transcompartmental proinflammatory response, the degree and differential kinetics of which suggests that the propagation of inflammation may depend on the primary site of injury.
KW - Acute Lung Injury
KW - Administration, Intravenous
KW - Adult
KW - Biological Markers
KW - Bronchoalveolar Lavage
KW - Double-Blind Method
KW - Drug Administration Routes
KW - Endotoxins
KW - Hemodynamics
KW - Humans
KW - Inflammation
KW - Inflammation Mediators
KW - Lipopolysaccharides
KW - Lung Diseases
KW - Male
KW - Pneumonia
KW - Systemic Inflammatory Response Syndrome
KW - Time Factors
U2 - 10.1097/CCM.0000000000000320
DO - 10.1097/CCM.0000000000000320
M3 - Journal article
C2 - 24732241
VL - 42
SP - 1658
EP - 1665
JO - Critical Care Medicine
JF - Critical Care Medicine
SN - 0090-3493
IS - 7
ER -
ID: 138503268