NEUTROPHIL ALVEOLITIS FOLLOWING ENDOTOXEMIA - ENHANCEMENT BY PREVIOUS EXPOSURE TO HYPEROXIA

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Abstract
Escherichia coli endotoxin, 2.5 mg/kg, was injected i.p. in rats, sequential quantified alveolar inflammation during a 6-day period by several techniques, and observed the effect of previous exposure to hyperoxia on the intensity of alveolitis in this model. As noted in other models of endotoxemia, intravascular sequestration of leukocytes and an increase in the retention of 125I albumin was found in the lung 4-6 h after the injection of endotoxin. Bronchoalveolar lavage fluid (BALF) obtained at this time only slightly stimulated the migration of neutrophils in vitro, and the numbers and types of cells recovered by lavage were normal. Fifteen h after the injection of endotoxin, however, bronchoalveolar lavage fluid stimulated both random and directed migration of neutrophils in vitro, although recovery of neutrophils by lavage was increased only slightly. By 24 h, 125I albumin retention had returned to normal levels, but the chemotactic activity of BALF remained high, and the percentage and absolute number of neutrophils recovered by lung lavage were increased markedly. The recovery of neutrophils remained significantly elevated for 3 days but declined to control levels by 6 days, whereas the recovery of alveolar macrophages was increased at this time. Exposure to 100% O2 for 36 h prior to endotoxemia accelerated and intensified neutrophil influx into the lung and increased the stimulatory effect of BALF on neutrophil migration in vitro. A single episode of endotoxemia in the rat evidently causes a multi-phasic alveolar inflammatory response, and that this response is accelerated and intensified by prior, mild exposure to hyperoxia. The results also raise the possibility that the early changes in lung vascular permeability caused by endotoxemia are dissociated in time from the migration of neutrophils from the pulmonary vasculature into the distal air spaces.