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Intrabronchial activated protein C enhances lipopolysaccharide-induced pulmonary responses.
MedLine Citation:
PMID:  23060625     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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).
Authors:
Liesbeth M Kager; J Daan de Boer; Paul Bresser; Jaring S van der Zee; Sacha Zeerleder; Joost C M Meijers; Cornelis van 't Veer; Tom van der Poll
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-11
Journal Detail:
Title:  The European respiratory journal : official journal of the European Society for Clinical Respiratory Physiology     Volume:  -     ISSN:  1399-3003     ISO Abbreviation:  Eur. Respir. J.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8803460     Medline TA:  Eur Respir J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The Netherlands, Center of Experimental and Molecular Medicine.
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