Circulating neutrophil kinetics during tolerance in hemorrhagic shock using bacterial lipopolysaccharide

The objective of this study was to investigate mechanisms by which circulating polymorphonuclear neutrophils (PMNs) may contribute to the tolerance to hemorrhagic shock induced by pretreatment with lipopolysaccharides (LPS). Tolerance was developed by daily injections of sublethal doses of LPS for four subsequent days while controls received saline injections. During shock, both groups of rats were maintained for 3 h at 40 mmHg mean arterial pressure and were then observed for survival during a 24-h period. This protocol resulted in 40% survival in the untreated controls and 89% survival in the tolerant group (P < 0.0068). Hypotension caused an initial neutropenia in both groups. The circulating PMN counts remained lower in the tolerant than in the controls rats for most of the low flow period. The number of circulating activated PMNs in whole blood, as assessed by spontaneous nitroblue tetrazolium reduction, was lower in tolerant animals before and during most of the hypotensive period, except immediately after bleeding when both groups have low circulating leukocyte counts. No detectable tumor necrosis factor activity was observed in the plasma of either group. Adhesion of circulating PMNs to nylon fibers in vitro and the number of PMNs adhering to the endothelium in the mesentery in vivo was significantly lower in the tolerant rats. We conclude that LPS pretreatment produces a reduction in the activated circulating PMNs and in the degree of PMN adhesion to endothelium with subsequent improvement of survival after hemorrhagic shock.