Neutrophil depletion does not prevent lung edema after endotoxin infusion in goats

Abstract

Neutropenia was produced in goats by injection of either nitrogen mustard, (1.5 mg/kg) or hydroxyurea (200 mg X kg-1 X day-1). A nitrogen mustard (M + E) group (n = 6), a hydroxyurea (H + E) group (n = 5), and a control (E) group (n = 7) were given 1-h infusions of endotoxin (5 micrograms/kg total dose), then monitored for up to 5 h. Postmortem extravascular lung water (EVLW) was significantly higher in the M + E group (14.2 +/- 4.4 ml/kg) and the E group (11.9 +/- 3.9 ml/kg) when compared with a normal control (6.6 +/- 1.3 ml/kg) group that did not receive endotoxin. EVLW in a group made neutropenic with nitrogen mustard (6.7 +/- 1.3 ml/kg) and the H + E (7.9 +/- 1.5 ml/kg) groups were not statistically different from each other or from normal controls. Circulating neutrophil counts averaged 32 +/- 42 cells/microliter in the M + E group and 180 +/- 210 cells/microliter in the H + E group. Only minimal histological changes were seen in the H + E group, but the E and M + E lungs had severe pulmonary edema. We conclude that neutrophils are not required for increased EVLW and decreased arterial O2 partial pressure after endotoxin infusion, and hydroxyurea prevents at least part of the pulmonary edema after endotoxin by a mechanism that is not neutrophil dependent.