Immunomodulatory Effects of Dexamethasone, Tocilizumab and Anakinra During Experimental Human Endotoxemia

Inclusion Criteria: * Male subjects aged ≥18 and ≤35 years * Body mass index (BMI) ≥18 and ≤30 kg/m2 * Healthy (as determined by medical history, physical examination, vital signs, 12-lead electrocardiogram and routine clinical laboratory parameters) * Able to comprehend and sign the Information letter and Informed Consent (IC) prior to enrolment in the study. Exclusion Criteria: * Use of any prescription medication or over-the-counter non-steroidal anti-inflammatory drugs * Known anaphylaxis or hypersensitivity to any (non-)investigational products or their excipients * History of chronic headache or previous post-dural puncture headache (PDPH) * History or signs of severe atopic syndrome (asthma, rhinitis with medication and/or eczema) * History of any disease associated with immune deficiency * History of cancer in the last 5 years (excluding localised skin cancer or carcinoma in situ) * History or signs of haematological disease * History or signs of thromboembolic disorders * History of peptic / gastric ulcer disease * History of psychiatric disorders * Thrombocytopenia (\<150\*109/mL) or anaemia (\<8.0 mmol/L) * History, signs or symptoms of cardiovascular disease, in particular: * Prone to vagal collapse * History of atrial or ventricular arrhythmia * Cardiac conduction abnormalities on the ECG consisting of a 2nd degree atrio-ventricular block or a complete left 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 (above 2x the upper limit of normal) * Signs of infection (CRP \> 20 mg/L, white blood cells \> 12x109/L or * lt; 4x109/L) * Clinically significant acute illness, including infections or trauma, within 1 month prior to the first LPS challenge * Previous (participation in a study with) endotoxin (LPS) administration * Participation in an experimental intervention or drug trial within 3 months prior to the first LPS challenge * Any vaccination or blood donation within 1 month prior to the first LPS challenge * Recent hospital admission or surgery with general anaesthesia within 3 months prior to the first LPS challenge * Use of recreational drugs within 2 weeks prior to the first LPS challenge * Suspected of not being able to comply with the trial protocol * Inability to personally provide written informed consent (e.g. for linguistic or mental reasons) and/or take part in the study