PT  - JOURNAL ARTICLE
AU  - Liesbeth M. Kager
AU  - J. Daan de Boer
AU  - Paul Bresser
AU  - Jaring S. van der Zee
AU  - Sacha Zeerleder
AU  - Joost C.M. Meijers
AU  - Cornelis van 't Veer
AU  - Tom van der Poll
TI  - Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses
AID  - 10.1183/09031936.00057112
DP  - 2013 Jul 01
TA  - European Respiratory Journal
PG  - 188--197
VI  - 42
IP  - 1
4099  - http://erj.ersjournals.com/content/42/1/188.short
4100  - http://erj.ersjournals.com/content/42/1/188.full
SO  - Eur Respir J2013 Jul 01; 42
AB  - Intravenous administration of activated protein C (APC) inhibits coagulation and inflammation in the lungs of humans and animals. Investigations in rodents demonstrated that direct intrapulmonary delivery of APC also exerts anticoagulant and anti-inflammatory effects. The effect of intrabronchial administration of recombinant human (rh)APC on lipopolysaccharide (LPS)-induced haemostatic and inflammatory alterations in the bronchoalveolar space of humans was studied. Eight subjects received rhAPC via intrabronchial instillation by bronchoscope, while in a contralateral subsegment subjects received saline; all subjects were challenged bilaterally with LPS in the same lung subsegments. Four additional subjects received rhAPC (75 μg), with saline as a control in the contralateral subsegment, while they were bilaterally “challenged” with saline. After 6 h a bronchoalveolar lavage was performed and coagulation and inflammatory parameters were measured. rhAPC enhanced LPS-induced coagulation activation in the bronchoalveolar space, when compared with the control side. In addition, rhAPC amplified LPS-induced pro-inflammatory responses, as indicated by higher concentrations of cytokines and chemokines. rhAPC alone did not have procoagulant or pro-inflammatory effects. Locally administered rhAPC has unexpected procoagulant and pro-inflammatory effects in LPS-challenged lung subsegments. These data argue against a role for intrapulmonary delivery of rhAPC as a treatment strategy for lung inflammatory disorders in humans.