Plasma-derived human C1-esterase inhibitor does not prevent mechanical ventilation-induced pulmonary complement activation in a rat model of Streptococcus pneumoniae pneumonia.
Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury.
Laboratory of Experimental Intensive Care and Anesthesiology (L·E·I·C·A), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands, f.m.debeer@amc.uva.nl.
F M
FM
de Beer
H
H
Aslami
J
J
Hoeksma
G
G
van Mierlo
D
D
Wouters
S
S
Zeerleder
J J T H
JJ
Roelofs
N P
NP
Juffermans
M J
MJ
Schultz
W K
WK
Lagrand
D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D050718:Complement C1 Inhibitor Protein / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000382:microbiology; D008297:Male; D011014:Pneumonia / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects*; D013296:Streptococcus pneumoniae / Q000502:physiology*; D013997:Time Factors; D055397:Ventilator-Induced Lung Injury / Q000209:etiology / Q000276:immunology / Q000517:prevention & control
D050718:Complement C1 Inhibitor Protein