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

Background: 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. Methods: Eighteen healthy non-atopic human subjects inhaled either 15 mu g (n = 10) or 50 mu g (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. Results: Acute flu-like symptoms and pyrexia were significantly greater in the 50 mu g than 15 mu g 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 mu g group. Myeloperoxidase, human neutrophil elastase and interleukin-8 in sputum sol., but not blood, showed a trend towards greater increase following 50 mu g LPS. All these changes were resolved at one week. In the 50 mu g dose group atone, there was a reduction in the proportion of peripheral blood interferon (IFN)-gamma-producing CD4+ and CD8+ T cells at 6 h followed by an increase at 1 week after inhaled LPS. Conclusions: 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-gamma-producing T cells into tissue from inhaled 50 mu g LPS, followed by reappearance of these cells in blood 1 week later. (c) 2005 Elsevier Ltd. All rights reserved.