Inhaled LPS induces blood release of Clara cell specific protein (CC16) in human beings.
BACKGROUND
Animal models of lung inflammation have validated the plasma 16-kd Clara cell protein (CC16) as a peripheral marker of the permeability of the alveolocapillary barrier.


OBJECTIVE
We investigated in human beings whether inhaled LPS induced a rise in airways permeability measured by the plasma changes in CC16.


METHODS
The CC16 was measured in plasma from 15 subjects exposed to LPS by inhalation, during which the kinetics and the dose-response relationship of LPS-induced CC16 were evaluated. Because LPS-induced response involves macrophages activation, the protective effect of oral methylprednisolone was also evaluated.


RESULTS
An inhalation of 50 microg LPS induced a significant ( P < .001) rise in CC16 after 6 hours (from 7.24 [+/-0.68] microg/L to 10.69 [+/-0.99] microg/L) that normalized at 24 hours (6.65 [+/-0.33] microg/L). The CC16 response was dose-related, with the no-response threshold 0.5 microg LPS. A 6-day treatment with 20 mg/d methylprednisolone inhibited significantly ( P < .001) the CC16 response to 50 microg LPS.


CONCLUSIONS
Exposure to LPS by inhalation in healthy subjects induces an intravascular leakage of CC16 that can be blocked by corticosteroids. These observations further validate plasma CC16 as a noninvasive test of the alveolocapillary barrier permeability.
Michel
Olivier
O
Clinics of Allergology and Respiratory Diseases, Saint-Pierre University Hospital, Free University of Brussels, Rue Haute 322, B-1000 Brussels, Belgium. omichel@ulb.ac.be
Murdoch
Robert
R
Bernard
Alfred
A
D000284:Administration, Oral; D015415:Biomarkers / Q000097:blood; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000008:administration & dosage; D004791:Enzyme Inhibitors / Q000097:blood*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology; D006801:Humans; D001239:Inhalation; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000037:antagonists & inhibitors; D008775:Methylprednisolone / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014598:Uteroglobin / Q000097:blood*
D015415:Biomarkers; D004785:Environmental Pollutants; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D008070:Lipopolysaccharides; C556389:SCGB1A1 protein, human; D014598:Uteroglobin; D008775:Methylprednisolone