Delayed cyclo-oxygenase blockade reduces the neutrophil respiratory burst and plasma tumor necrosis factor levels in sepsis-induced acute lung injury.
Ibuprofen pretreatment attenuates the enhanced neutrophil (PMN) respiratory burst and reduces increased plasma tumor necrosis factor (TNF) activity in porcine sepsis-induced acute lung injury (ALI). These septic responses have been linked to increased alveolar-capillary membrane (ACM) permeability. This study was designed to establish whether delayed ibuprofen treatment would have the same effect and to examine the relationship between PMN oxidant generation and TNF. Three groups of anesthetized, ventilated pigs (15-25 kg) were used. Group Ps received Pseudomonas aeruginosa (5 x 10(8) CFU/mL at 0.3 mL/20 kg/min) for one hour IV; The control group (Con) received 0.9% NaCl. Group D-Ibu received ibuprofen 12.5 mg/kg as a delayed bolus at 30 minutes and again at 120 minutes after Ps. Protein (BAL-P, microgram/mL) in harvested bronchoalveolar lavage fluid and extravascular lung water (EVLW, mL/kg) were used to estimate the integrity of the ACM. Superoxide anion (O2-) generation (ferricytochrome c reduction) from circulating PMNs and plasma TNF activity (L929 fibroblast bioassay) were measured. The EVLW increased significantly (p less than 0.05), as did BAL-P (p less than 0.01), in the P. aeruginosa-treated animals at 300 minutes. These increases were abolished in Group D-Ibu: EVLW, 6.6 +/- 1.0 baseline vs. 14.6 +/- 2.6 Ps 300 vs. 6.8 +/- 0.9 D-Ibu 300; BAL-P, 175 +/- 28 baseline vs. 984 +/- 186 Ps 300 vs. 284 +/- 42.8 D-Ibu 300. Both enhanced PMN oxidant activity and increased plasma TNF activity were significantly attenuated by delayed ibuprofen treatment. These data support the efficacy of the nonsteroidal anti-inflammatory drug, ibuprofen, when used after the onset of a septic stimulus.
Carey
P D
PD
Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond 23229.
Leeper-Woodford
S K
SK
Walsh
C J
CJ
Byrne
K
K
Fowler
A A
AA
Sugerman
H J
HJ
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002199:Capillary Permeability; D016861:Cyclooxygenase Inhibitors; D015633:Extravascular Lung Water / Q000378:metabolism; D006439:Hemodynamics; D007052:Ibuprofen / Q000494:pharmacology; D007958:Leukocyte Count; D008168:Lung / Q000098:blood supply; D008171:Lung Diseases / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D011552:Pseudomonas Infections / Q000150:complications*; D011650:Pulmonary Alveoli / Q000503:physiopathology; D013481:Superoxides / Q000378:metabolism; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D016861:Cyclooxygenase Inhibitors; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D013755:Tetradecanoylphorbol Acetate; D007052:Ibuprofen