NCT00246714

Pathophysiology and Clinical Relevance of Endotoxin Tolerance in Humans

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 16 (estimated)
• Sponsor: Radboud University Medical Center · Academic / Other
• Sex: Male
• Age: 18 Years – 35 Years
• Healthy volunteers: Accepted

Summary

A number of diseases lead to a so called systemic inflammatory response syndrome (SIRS). This excessive response is self-destructive and leads to major complications of the initial disease: dysfunction of the microcirculation, systemic vasodilation, and increased capillary leakage and oedema. Animal studies have shown that pre-treatment with endotoxin (lipopolysaccharide or LPS) suppress the excessive immune response and when rechallenged, the animal survive a normally lethal dose of endotoxin. Besides a diminished cytokine response, an increased production of leucocytes in the bone marrow and an increased phagocytosis after pre-treatment with endotoxin is seen. The combination of these factors: diminished systemic inflammatory response and increased cellular immunity makes that endotoxin tolerance is a useful tool for preventing the complications after an excessive inflammatory response. Further, the presence of cross-tolerance has also been shown: Endotoxin tolerant mice survive more after induction of a normally lethal fungal infection. Endotoxin tolerance is also protective for ischemia/reperfusion injury in kidneys, heart and liver. Little data is known about endotoxin tolerance in human. The purpose of this study is to induce a state of tolerance through 2 different administration schedules and monitor the effect of tolerance on pro- and anti-inflammatory cytokines, other inflammatory parameters and different proteins involved in the signalling pathway. The effects of tolerance on vascular reactivity will be determined. Finally, the effect of tolerance on ischemia-reperfusion injury will be investigated.

Detailed description

See protocol

Conditions

• Endotoxemia

Interventions

Type	Name	Description
DRUG	repeated injections of endotoxin during 5 days

Timeline

• Start date: 2005-10-01
• Primary completion: 2007-12-01
• Completion: 2007-12-01
• First posted: 2005-10-31
• Last updated: 2008-04-15

Locations

1 site across 1 country: Netherlands