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Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Endotoxin in concentrated coarse and fine ambient particles induces acute systemic inflammation in controlled human
Behrooz Behbod1, Bruce Urch, Mary Speck
1Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Background:
Knowledge of the inhalable particulate matter components responsible for health effects is important for developing targeted regulation.
Objectives:
In a double-blind randomised cross-over trial of controlled human exposures to concentrated ambient particles (CAPs) and their endotoxin and (1→3)-β-D-glucan components, we evaluated acute inflammatory responses.
Methods:
35 healthy adults were exposed to five 130-min exposures at rest: (1) fine CAPs (~250 µg/m(3)); (2) coarse CAPs (200 µg/m(3)); (3) second coarse CAPs (~200 µg/m(3)); (4) filtered air; and (5) medical air. Induced sputum cell counts were measured at screening and 24 h postexposure. Venous blood total leucocytes, neutrophils, interleukin-6 and high-sensitivity C reactive protein (CRP) were measured pre-exposure, 3 and 24 h postexposure.
Results:
Relative to filtered air, an increase in blood leucocytes 24 h (but not 3 h) postexposure was significantly associated with coarse (estimate=0.44×10(9) cells/L (95% CI 0.01 to 0.88); n=132) and fine CAPs (0.68×10(9) cells /L (95% CI 0.19 to 1.17); n=132), but not medical air. Similar associations were found with neutrophil responses. An interquartile increase in endotoxin (5.4 ng/m(3)) was significantly associated with increased blood leucocytes 3 h postexposure (0.27×10(9) cells/L (95% CI 0.03 to 0.51); n=98) and 24 h postexposure (0.37×10(9) cells/L (95% CI 0.12 to 0.63); n=98). This endotoxin effect did not differ by particle size. There were no associations with glucan concentrations or interleukin-6, CRP or sputum responses.
Conclusions:
In healthy adults, controlled coarse and fine ambient particle exposures independently induced acute systemic inflammatory responses. Endotoxin contributes to the inflammatory role of particle air pollution.
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