The effects of two antiinflammatory pretreatments on bacterial-induced lung injury

Background: Two antiinflammatory therapies that have been effective in prev enting 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 documen ted previously. Methods: New Zealand white rabbits were anesthetized and three pretreatment s were administered: (1) pentoxifylline pretreatment (a 20-mg/kg bolus dose and then 6 mg . kg(-1) . h(-1) given intravenously), (2) 1 ml anti-tumor n ecrosis factor alpha antiserum given intravenously, or (3) normal saline gi ven 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 mech anical 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 pret reated, 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 in jury, the pentoxifylline pretreatment but not the anti-tumor necrosis facto r alpha pretreatment prevented much of the bacteria-induced lung injury, Pe ntoxifylline pretreatment significantly improved the measurements of left l ung edema and epithelial and endothelial permeability, There was also a tre nd for improved oxygenation in the pentoxifylline pretreated and infected a nimals, In contrast, the anti-tumor necrosis factor a pretreatment did not prevent the 1,bacteria induced lung Injury and increased some of the measur ements of lung injury. Conclusions: Two antiinflammatory therapies that prevented acid-induced lun g injury to the noninstilled left lungs had significantly different effects on a subsequent bacteria induced lung injury to the left lungs. The therap ies differed in their mechanism of tumor necrosis factor alpha blockade, an d tills mag: have affected the bacteria induced injury to the lungs.