Healthy subjects express differences in clinical responses to inhaled lipopolysaccharide that are related with inflammation and with atopy.
BACKGROUND
Endotoxin and its purified derivative LPS are important contaminants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable interindividual variability in LPS sensitivity.


OBJECTIVE
The aim of the study was to relate the individual clinical responses to inhaled LPS with the inflammatory process and the atopic status.


METHODS
Fifteen healthy subjects were challenged each week by inhalation with saline solution or LPS (0.5, 5, or 50 microg). The systemic response was defined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selectin. The LPS-induced airway response was defined as the increase in airway responsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The atopic status was defined as an increase in IgE or a positive skin prick test result.


RESULTS
Subjects (n = 7) with a significant increase in body temperature had a larger increase in the systemic inflammatory response (blood neutrophilia; P <.01) and in blood concentrations of C-reactive protein (P <.02) and LBP (P <.01). Subjects with a significant increase in airway responsiveness (n = 8) had an increase in the sputum concentration of eosinophil cationic protein (P <.01). The amplitude of the systemic response (increase in body temperature [P <.001], blood neutrophilia [P <.02], and rise in LBP [P <.05] and decrease in FEV(1) [P <.01]) were inversely associated with the atopic status, suggesting a link between atopy and LPS responsiveness.


CONCLUSIONS
The clinical response to LPS occurs systemically or locally and is associated with inflammation. The atopic status was inversely related to the systemic inflammation.
Michel
O
O
Clinics of Allergology and Respiratory Diseases, Saint-Pierre University Hospital, and the Clinic of Haematology, CHU Brugmann (Free University of Brussels), Brussels, Belgium.
Dentener
M
M
Corazza
F
F
Buurman
W
W
Rylander
R
R
D000209:Acute-Phase Proteins / Q000032:analysis; D000210:Acute-Phase Reaction / Q000139:chemically induced; D000280:Administration, Inhalation; D000328:Adult; D015415:Biomarkers; D001798:Blood Proteins / Q000032:analysis; D016535:Bronchial Hyperreactivity / Q000139:chemically induced; D047091:Eosinophil Granule Proteins; D005260:Female; D005334:Fever / Q000139:chemically induced; D005541:Forced Expiratory Volume; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D007073:Immunoglobulin E / Q000096:biosynthesis; D007249:Inflammation / Q000276:immunology*; D007964:Leukocytosis / Q000139:chemically induced; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology* / Q000494:pharmacology; D008297:Male; D009504:Neutrophils; D012260:Ribonucleases; D012471:Salivary Proteins and Peptides / Q000032:analysis
D000209:Acute-Phase Proteins; D015415:Biomarkers; D001798:Blood Proteins; D047091:Eosinophil Granule Proteins; D008070:Lipopolysaccharides; D012471:Salivary Proteins and Peptides; D007073:Immunoglobulin E; D012260:Ribonucleases