Transcompartmental Inflammatory Responses in Humans: IV Versus Endobronchial Administration of Endotoxin

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

SN - 0090-3493

VL - 42

SP - 1658

EP - 1665

JO - Critical Care Medicine

JF - Critical Care Medicine

IS - 7

ER -