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Dose-response relationship to inhaled endotoxin in normal subjects
O Michel1, A M Nagy, M Schroeven
1Clinic of Allergology and Respiratory Diseases, Saint-Pierre University Hospital (ULB), Brussels, Belgium. omichel@resulb.ulb.ac.be
American Journal of Respiratory and Critical Care Medicine
|November 14, 1997
Summary
Exposure to lipopolysaccharide (LPS) can cause lung inflammation. Inhaling less than 0.5 microg of LPS in healthy individuals showed no adverse effects, with higher doses causing dose-dependent inflammatory responses.
Area of Science:
- Pulmonary Medicine
- Immunology
- Toxicology
Background:
- Lipopolysaccharide (LPS) exposure is linked to occupational lung diseases and severe asthma.
- Understanding LPS inhalation dose-response in healthy individuals is crucial for setting safety exposure limits.
Purpose of the Study:
- To evaluate the clinical and inflammatory responses to increasing doses of inhaled LPS in normal subjects.
- To identify sensitive biomarkers for LPS-induced inflammation.
Main Methods:
- Nine healthy volunteers inhaled saline, 0.5, 5, or 50 microg of LPS weekly.
- Measured clinical symptoms, fever, FEV1, blood polymorphonuclear neutrophils (PMNs) and their activation, C-reactive protein (CRP), and sputum inflammatory markers (MPO, ECP, TNF-alpha).
Main Results:
- Inhalation of 0.5 microg LPS showed no significant inflammatory response.
- 5 microg LPS inhalation led to increased blood CRP and PMNs, and elevated sputum PMNs, monocytes, and MPO.
- 50 microg LPS inhalation caused fever, increased blood PMNs, blood/urine CRP, and sputum PMNs, monocytes, lymphocytes, MPO, TNF-alpha, and ECP, with five subjects developing symptoms.
Conclusions:
- Inhaled LPS elicits a dose-dependent inflammatory response in healthy individuals.
- Blood PMN count and activation, blood CRP, and sputum PMN count are sensitive markers of LPS-induced inflammation.
- The no-response threshold for acute LPS inhalation in normal subjects is below 0.5 microg.