Low-dose endotoxin inhalation in healthy volunteers--a challenge model for early clinical drug development.

ABSTRACT:

Background

Inhalation of endotoxin (LPS) induces a predominantly neutrophilic airway inflammation and has been used as model to test the anti-inflammatory activity of novel drugs. In the past, a dose exceeding 15-50 μg was generally needed to induce a sufficient inflammatory response. For human studies, regulatory authorities in some countries now request the use of GMP-grade LPS, which is of limited availability. It was therefore the aim of this study to test the effect and reproducibility of a low-dose LPS challenge (20,000 E.U.; 2 μg) using a flow- and volume-controlled inhalation technique to increase LPS deposition.

Methods

Two to four weeks after a baseline sputum induction, 12 non-smoking healthy volunteers inhaled LPS on three occasions, separated by at least 4 weeks

SUBMITTER: Janssen O 

PROVIDER: S-EPMC3635929 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature