1. We have studied the time course of the numbers of arterial monocytes and their superoxide anion (O2−) production in a chronically instrumented sheep model of subacute endotoxaemia induced by a continuous intravenous infusion of Escherichia coli lipopolysaccharide (20 ng min−1 kg−1).
2. Four out of 11 animals died from irreversible respiratory and cardiovascular failure within 21 h of the start of lipopolysaccharide administration ('non-survivors'), whereas in the seven surviving sheep ('survivors') there was a persistence of decreased systemic vascular resistance, systemic hypotension, pulmonary hypertension, anorexia and lethargy.
3. O2− generation by isolated monocytes was measured by the O2− dismutase-inhibitable reduction of ferricytochrome c after stimulation with phorbol myristate acetate (100 ng/ml) or opsonized zymosan (3 mg/ml). Basal mean value of phorbol myristate acetate-stimulated O2− production was significantly (P = 0.008) higher for non-survivors (31.3 ± 8.8 nmol 30 min−1 10−6 cells; n = 4) than for survivors (6.2 ± 2.3 nmol 30 min−1 10−6 cells; n = 7).
4. For both survivors and non-survivors, monocyte counts and phorbol myristate acetate-stimulated O2− production increased over time to reach in survivors a plateau after 2 days of continuous lipopolysaccharide infusion. Similar results were obtained when monocytes were stimulated for O2− production with opsonized zymosan.
5. These results suggest that (1) increased O−2 production by monocytes and monocytosis appear with a precise, delayed time course during the development of subacute endotoxaemia in sheep; and (2) a high stimulated O2− production by monocytes before lipopolysaccharide administration may represent a predictive factor for the subsequent respiratory failure and outcome of endotoxaemia.
