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Variable airway responsiveness to inhaled lipopolysaccharide
J N Kline1, J D Cowden, G W Hunninghake
1Departments of Medicine, Pediatrics, and Preventive Medicine, University of Iowa College of Medicine, Department of Veterans Affairs Medical Center, Iowa City, Iowa, USA. joel-kline@uiowa.edu
Summary
Individuals respond differently to inhaled lipopolysaccharide (LPS), a component of organic dust. Some are sensitive, experiencing lung function decline, while others are hyporesponsive, showing no significant changes, indicating a reproducible LPS response phenotype.
Area of Science:
- Immunology
- Pulmonary Medicine
- Environmental Health
Background:
- Inhaled endotoxin (lipopolysaccharide [LPS]) exposure can trigger airway symptoms and asthma exacerbations.
- Occupational exposure to organic dusts links airflow obstruction progression to endotoxin concentration.
- Individual responses to LPS exposure vary significantly.
Purpose of the Study:
- To investigate differential human responses to inhaled lipopolysaccharide (LPS).
- To determine if LPS inhalation elicits a reproducible phenotype in healthy volunteers.
Main Methods:
- 72 healthy volunteers were challenged with increasing doses of LPS.
- Lung function (FEV1) was monitored, with study termination upon a >/= 20% decline.
- Reproducibility was assessed through serial testing.
- Cytokine release (IL-6, IL-8) from monocytes was compared between sensitive and hyporesponsive groups.
Main Results:
- Significant inter-individual variability in LPS response was observed.
- Eight 'sensitive' subjects showed FEV1 decline with ≤6.5 µg LPS.
- Eleven 'hyporesponsive' subjects maintained FEV1 with up to 41.5 µg LPS.
- LPS response was reproducible across serial tests.
- Sensitive subjects were more often female; hyporesponsive subjects were more often male.
- Hyporesponsive subjects' monocytes released less IL-6 and IL-8 compared to sensitive subjects.
Conclusions:
- A reproducible LPS inhalation response phenotype exists in humans.
- This phenotype is associated with sex and differential monocyte cytokine production.
- Identifies an opportunity to study genetic factors influencing LPS response.