Recombinant human Activated Protein C (rhAPC) has been shown to reduce the mortality of patients with severe sepsis. The biological effects of APC are pleiotropic, and can be roughly divided in anticoagulant and cytoprotective effects. Lung infection and inflammation are associated with reduced bronchoalveolar levels of endogenous APC. Recent evidence derived from animal studies indicates that local administration of rAPC into the lungs exerts local anti-inflammatory and anticoagulant effects. In this study we propose to study the potential of locally administered APC, within a lung subsegment, to inhibit lipopolysaccharide (LPS) induced lung inflammation and coagulation in humans.

Inclusion Criteria:

• Male, 18-35 years of age
• No clinically significant findings during physical examination and hematological and biochemical screening
• Normal spirometry and ECG
• Able to communicate well with the investigator and to comply with the requirements of the study
• No medication
• Written informed consent
• No smoking

Exclusion criteria:

• Known diseases
• A history of smoking within the last six months, or regular consumption of greater than three units of alcohol per day
• Administration of any investigational drug within 30 days of study initiation
• Donation of blood within 60 days, or loss of greater than 400 ml of blood within 12 weeks of study initiation
• History of enhanced bleeding tendency
• History of heparin-induced thrombocytopenia
• History of serious drug-related reactions, including hypersensitivity