TY - JOUR T1 - Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses JF - European Respiratory Journal JO - Eur Respir J SP - 188 LP - 197 DO - 10.1183/09031936.00057112 VL - 42 IS - 1 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 Y1 - 2013/07/01 UR - http://erj.ersjournals.com/content/42/1/188.abstract N2 - 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. ER -