%0 Journal Article %A Liesbeth M. Kager %A J.D. De Boer %A Paul Bresser %A Jaring S. van der Zee %A Sacha Zeerleder %A Joost C. M. Meijers %A Cornelis van 't Veer %A Tom van der Poll %T Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses %D 2012 %R 10.1183/09031936.00057112 %J European Respiratory Journal %P erj00571-2012 %X 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 hemostatic 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 control in the contralateral subsegment, while they were bilaterally “challenged” with saline. After 6 hours 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 control side. In addition, rhAPC amplified LPS-induced proinflammatory responses, as indicated by higher concentrations of cytokines and chemokines. RhAPC alone did not have procoagulant or proinflammatory effects.Locally administered rhAPC has unexpected procoagulant and proinflammatory 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. (ClinicalTrials.gov number: NCT00943267; Nederlands Trial register number: NTR1544). %U https://erj.ersjournals.com/content/erj/early/2012/11/08/09031936.00057112.full.pdf