The effects of two antiinflammatory pretreatments on bacterial-induced lung injury.
BACKGROUND
Two antiinflammatory therapies that have been effective in preventing acid-induced lung injury were evaluated. Specifically, their effects on a subsequent bacterial-airspace challenge were compared. Bacteria were instilled 24 h after acid-induced lung injury. Pseudomonas aeruginosa PAO-1 was used as the bacteria, because its effects in healthy lungs was documented previously.


METHODS
New Zealand white rabbits were anesthetized and three pretreatments were administered: (1) pentoxifylline pretreatment (a 20-mg/kg bolus dose and then 6 mg x kg(-1) x h(-1) given intravenously), (2) 1 ml anti-tumor necrosis factor alpha antiserum given intravenously, or (3) normal saline given intravenously. The pretreatment doses were shown previously to prevent acid-induced lung injury. Then 1.2 ml/kg hydrochloric acid (HCl), pH 1.25, was instilled into the rabbits' right lungs. All the animals underwent mechanical ventilation for 8 h. Twenty-four hours after the acid instillation, the rabbits were anesthetized again and 2 ml/kg (10(9) colony forming units/ml) PAO-1 was instilled into their left lungs. The rabbits' breathing was aided by mechanical ventilation for another 8 h, and then they were killed and exsanguinated.


RESULTS
Both pretreatments attenuated the acid-induced lung injury of the noninstilled left lungs. Arterial oxygen tension and the lung edema of pretreated, acid-exposed animals were significantly and almost equally improved (compared with no pretreatments) by either of the pretreatments. However, when the bacteria were instilled into the left lungs 24 h after the acid injury, the pentoxifylline pretreatment but not the anti-tumor necrosis factor alpha pretreatment prevented much of the bacteria-induced lung injury. Pentoxifylline pretreatment significantly improved the measurements of left lung edema and epithelial and endothelial permeability. There was also a trend for improved oxygenation in the pentoxifylline-pretreated and infected animals. In contrast, the anti-tumor necrosis factor alpha pretreatment did not prevent the bacteria-induced lung injury and increased some of the measurements of lung injury.


CONCLUSIONS
Two antiinflammatory therapies that prevented acid-induced lung injury to the noninstilled left lungs had significantly different effects on a subsequent bacteria-induced lung injury to the left lungs. The therapies differed in their mechanism of tumor necrosis factor alpha blockade, and this may have affected the bacteria-induced injury to the lungs.
Miyazaki
H
H
Cardiovascular Research Institute, University of California, San Francisco, USA.
Broaddus
V C
VC
Wiener-Kronish
J P
JP
Sawa
T
T
Pittet
J F
JF
Kravchenko
V
V
Mathison
J C
JC
Nishizawa
H
H
Hattori
S
S
Yamakawa
T
T
Yamada
H
H
Kudoh
I
I
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000517:prevention & control*; D006041:Goats; D007106:Immune Sera / Q000276:immunology; D016209:Interleukin-8 / Q000032:analysis; D008171:Lung Diseases / Q000517:prevention & control*; D008297:Male; D010100:Oxygen / Q000097:blood; D010431:Pentoxifylline / Q000627:therapeutic use*; D009195:Peroxidase / Q000032:analysis; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D007106:Immune Sera; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D010100:Oxygen; D010431:Pentoxifylline