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 contami nants of both domestic and occupational environments that have been related to airway diseases. A body of data suggests that there is considerable int erindividual variability in LPS sensitivity. Objective: The aim of the study was to relate the individual clinical respo nses to inhaled LPS with the inflammatory process and the atopic status. Methods: Fifteen healthy subjects were challenged each week by inhalation,v ith saline solution or LPS (0.5, 5, or 50 mug). The systemic response was d efined by the increase in body temperature, blood neutrophilia, acute-phase proteins (C-reactive protein and LPS-binding protein [LBP]), and E-selecti n. The LPS-induced airway response was defined as the increase in airway re sponsiveness and related to the cell count and concentration of TNF-alpha, myeloperoxidase, and eosinophil cationic protein in induced sputum. The ato pic 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 h ad a larger increase in the systemic inflammatory response (blood neutrophi lia; P < .01) and in blood concentrations of C-reactive protein (P < .02) a nd LBP (P < .01). Subjects with a significant increase in airway responsive ness (n = 8) had an increase in the sputum concentration of eosinophil cati onic 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, [P < .01]) were inversely associated with t he atopic status, suggesting a link between atopy and LPS responsiveness. Conclusions: The clinical response to LPS occurs systemically or locally an d is associated with inflammation. The atopic status was inversely related to the systemic inflammation.