Ibuprofen attenuates hypochlorous acid production from neutrophils in porcine acute lung injury.
Hypochlorous acid (HOCl), a neutrophil-generated oxidant, has been implicated in tissue destruction in sepsis-induced acute lung injury (ALI). Ibuprofen, a cyclooxygenase inhibitor, successfully attenuates many of the physiological derangements in ALI. The aim of this study was to examine the role of PMN hypochlorous acid in sepsis-induced ALI and evaluate the effect of ibuprofen therapy. Neutrophils from three groups of young (15-25 kg), anesthetized swine were studied: controls (C, n = 7) received 0.9% NaCl, septic animals (Ps, n = 8) received live Pseudomonas aeruginosa (5 x 10(8) CFU/ml at 0.3 ml/20 kg/min) for 60 min, and ibuprofen-treated animals (Ps + I, n = 6) received Ps plus ibuprofen 12.5 mg/kg administered at 0 and 120 min. Neutrophils were isolated from peripheral blood at 0, 60, and 300 min and the rate and total production of HOCl were assessed on the basis of the ability of the amino acid taurine to trap HOCl.


RESULTS
Septic (Ps) PMNs produce 32% more HOCl, P less than 0.01, at 300 min than at baseline which was associated with a marked increase in both extravascular lung water (6.44 +/- 0.8 ml/kg, t = 0 vs 16.03 +/- 2.6 ml/kg, t = 300, P less than 0.01) and bronchoalveolar protein content (115 +/- 13 micrograms/ml, t = 0 vs 633 +/- 104 micrograms/ml, t = 300, P less than 0.01). Ibuprofen significantly attenuated (P less than 0.05) HOCl production when compared to Ps, in conjunction with significantly (P less than 0.05) reduced levels of extravascular lung water and bronchoalveolar lavage protein.
Carey
P D
PD
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Byrne
K
K
Jenkins
J K
JK
Sielaff
T D
TD
Walsh
C J
CJ
Fowler
A A
AA
Sugerman
H J
HJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000378:metabolism; D002199:Capillary Permeability; D016861:Cyclooxygenase Inhibitors; D015633:Extravascular Lung Water / Q000378:metabolism; D006997:Hypochlorous Acid / Q000097:blood*; D007052:Ibuprofen / Q000627:therapeutic use*; D007958:Leukocyte Count; D008171:Lung Diseases / Q000097:blood* / Q000188:drug therapy / Q000209:etiology; D009504:Neutrophils / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011552:Pseudomonas Infections; D018805:Sepsis / Q000150:complications; D013552:Swine
D016861:Cyclooxygenase Inhibitors; D011506:Proteins; D006997:Hypochlorous Acid; D007052:Ibuprofen