Inhaled endotoxin in healthy human subjects: A dose-related study on systemic effects and peripheral CD4+ and CD8+ T cells

• Published in: Respiratory medicine 2006-03, Vol.100 (3), p.519-528
• Main Authors: Loh, L.C., Vyas, B., Kanabar, V., Kemeny, D.M., O’Connor, B.J.
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Adult; Biological and medical sciences; CD4; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - metabolism; CD8; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - metabolism; Dose-Response Relationship, Drug; Female; Human subjects; Humans; Inhaled endotoxin; Intracellular flow cytometry; Lipopolysaccharide; Lipopolysaccharides - administration & dosage; Lipopolysaccharides - adverse effects; Lymphocyte Count; Lymphocytes; Male; Medical sciences; Pneumology; Recruitment; Rodents; Sputum; Sputum - cytology
• ISSN: 0954-6111; 1532-3064
• DOI: 10.1016/j.rmed.2005.06.003

Inhaled endotoxin or lipopolysaccharide (LPS) is implicated in the pathogenesis of pulmonary diseases. We investigated the inhalation effects of two different doses of LPS in healthy human subjects. Eighteen healthy non-atopic human subjects inhaled either 15 μg ( n = 1 0 ) or 50 μg ( n = 8 ) Escherichia coli LPS in an open study. As control, each subject had isotonic saline inhalation 1 week before (baseline) and after LPS inhalation. Data collected included those of clinical parameter, induced sputum and peripheral blood CD4+ and CD8+ T cells. Acute flu-like symptoms and pyrexia were significantly greater in the 50 μg than 15 μg LPS group. Similarly, the increase in sputum and blood total cell and neutrophil counts at 6 h following inhaled LPS were greater in the 50 μg group. Myeloperoxidase, human neutrophil elastase and interleukin-8 in sputum sol, but not blood, showed a trend towards greater increase following 50 μg LPS. All these changes were resolved at one week. In the 50 μg dose group alone, there was a reduction in the proportion of peripheral blood interferon (IFN)- γ-producing CD4+ and CD8+ T cells at 6 h followed by an increase at 1 week after inhaled LPS. The airway and systemic effects of inhaled LPS are dose-related and predominantly neutrophilic. The changes in the proportions of circulating CD4+ and CD8+ T cells suggests preferential recruitment of IFN- γ-producing T cells into tissue from inhaled 50 μg LPS, followed by reappearance of these cells in blood 1 week later.