Determining the fingerprint of endotoxin tolerance

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 100

Inclusion Criteria

* Written informed consent
* Age *18 and *35 yrs
* Healthy (as confirmed by medical history, physical examination,
electrocardiography, laboratory tests)

Exclusion Criteria

* Pregnancy (confirmed by negative result of pregnancy tests prior to both
endotoxin challenges)
* Use of any medication
* Smoking
* History or signs of atopic syndrome (asthma, rhinitis with medication and/or
eczema)
* Known anaphylaxis or hypersensitivity to the non-investigational products or
their excipi-ents.
* History or signs of hematological disease:
* Thrombocytopenia (<150*10^9/ml) or anemia (for males: hemoglobin < 8.0 mmol/L
and for females: hemoglobin < 7.4 mmol/L)
* Abnormalities in leukocyte differential counts
* History, signs or symptoms of cardiovascular disease, in particular:
* Previous spontaneous vagal collapse
* History of atrial or ventricular arrhythmia
* Cardiac conduction abnormalities on the ECG consisting of a 2nd degree
atrioventricular block or a complete left bundle branch block
* Hypertension (defined as RR systolic > 160 or RR diastolic > 90)
* Hypotension (defined as RR systolic < 100 or RR diastolic < 50)
* Renal impairment (defined as plasma creatinine >120 *mol/l)
* Liver enzyme abnormalities (above 2x the upper limit of normal)
* Medical history of any disease associated with immune deficiency
* Signs of infection (CRP > 20 mg/L, WBC > 12x109/L or < 4 x109/L)
* Clinically significant acute illness, including infections, within 1 month of
the first endotoxin challenge
* Previous (participation in a study with) endotoxin (LPS) administration
* Any vaccination within 3 months within of the first endotoxin challenge
* Participation in a drug trial or donation of blood within 3 months prior to
first endotoxin challenge
* Recent hospital admission or surgery with general anesthesia within 3 months
prior to first endotoxin challenge
* Use of recreational drugs within 1 month of the first endotoxin challenge
* Inability to personally provide written informed consent (e.g. for linguistic
or mental rea-sons) and/or take part in the study.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Single-nucleotide polymorphisms (SNPs), genome-wide differential mRNA<br /><br>expression of monocytes obtained before and 4 hours after the first endotoxin<br /><br>challenge, and plasma cytokine concentration profiles upon the first and second<br /><br>endotoxin challenge (including but not limited to TNF*, IL-6, IL-8, and IL-10)<br /><br>to determine extent of endotoxin tolerance (which is expressed as the decrease<br /><br>in plasma cytokine levels between the first and second endotoxin challenge).<br /><br>These data will be integrated to determine the SNPs/transcripts that are<br /><br>predictive of the extent of endotoxin tolerance developed by the subjects.</p><br>

Secondary Outcome Measures