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

The goal of this clinical trial is to investigate the immunomodulatory effects of the drugs dexamethasone, tocilizumab and anakinra in healthy male subjects aged 18 to 35 undergoing experimental endotoxemia. The main questions it aims to answer are:

* What are the effects of these drugs on the development of immunoparalysis in a repeated human endotoxemia model? * What is the extent of the neuroinflammatory response and how do these drugs affect neuroinflammation in a repeated human endotoxemia model?

Researchers will compare these drugs to a placebo (a look-alike substance that contains no drug).

Participants will visit the Intensive Care research department on two or five occasions (screening included):

* The intervention group will receive an LPS challenge twice, with a week in between. Before the first LPS challenge, one of the described drugs will be administered. Blood, saliva and tear fluid will be collected regularly during the LPS challenge. Cerebrospinal fluid will also be collected through a catheter in the spinal cord. * The control group will not receive an LPS challenge or drug administration and will have only one study day. During this day, blood, saliva, tear fluid and cerebrospinal fluid will be collected as regularly as during the LPS challenge of the intervention group.

During an LPS challenge, the investigators mimic blood poisoning by giving an endotoxin, also called LPS. This is a small part of the cell wall of a bacteria. This will cause transient flu-like symptoms for 3-4 hours.