Effects of Oxygen Status on Hypoxia Inducible Factor 1-α and Inflammation. A Pilot Proof of Principle Study.

It has been shown in in vitro and animal models that hypoxia can have pro-inflammatory effects and hyperoxia can have anti-inflammatory effects. The pro-inflammatory effect could be the result of activation of Hypoxia Inducible Factor, a transcription factor that is known to activate many cell systems aimed at cell survival, including the inflammatory response. The anti-inflammatory effects of hyperoxia could be the annihilation of Hypoxia Inducible Factor, but also a decrease in inflammation due to oxygen toxicity resulting in a decrease in clearance of pathogens. These effects have been sparsely studied in humans. Therefore, we hypothesize that hypoxia results in an increase in Hypoxia Inducible Factor in circulating leukocytes and increases inflammatory reactions, whereas hyperoxia decreases these reactions.

Inclusion Criteria:

• Age ≥18 and ≤35 yrs
• Male
• Healthy

Exclusion Criteria:

• Use of any medication
• Smoking
• History, signs or symptoms of cardiovascular disease
• History of atrial or ventricular arrhythmia
• (Family) history of myocardial infarction or stroke under the age of 65 years
• Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrioventricular block or a complex bundle branch block
• Hypertension (defined as RR systolic > 160 or RR diastolic > 90 mmHg)
• Hypotension (defined as RR systolic < 100 or RR diastolic < 50 mmHg)
• Renal impairment (defined as plasma creatinine >120 μmol/l)
• Liver enzyme abnormalities alkaline phosphatase>230 U/L and/or ALT>90 U/L
• Medical history of any obvious disease associated with immune deficiency
• CRP > 20 mg/L, WBC > 12x109/L, or clinically significant acute illness, including infections, within 4 weeks before endotoxemia day
• Participation in a drug trial or donation of blood 3 months prior to the experiment
• Pre-existent lung disease or asthma
• Use of recreational drugs within 21 days prior to experiment day
• Visit to altitude >1500m within 4 weeks prior to the experiment
• Air travel with flight time over 3 hours within 4 weeks prior to the experiment
• History of acute mountain sickness
• Recent hospital admission or surgery with general anaesthesia (<3 months)
• Claustrophobia
• Feelings of discomfort during a 10 minute test wearing the transparent respiratory helmet at the screening visit