CIRCULATING NEUTROPHIL KINETICS DURING TOLERANCE IN HEMORRHAGIC-SHOCKUSING BACTERIAL LIPOPOLYSACCHARIDE

The objective of this study was to investigate mechanisms by which cir culating polymorphonuclear neutrophils (PMNs) may contribute to the to lerance to hemorrhagic shock induced by pretreatment with lipopolysacc harides (LPS). Tolerance was developed by daily injections of subletha l 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 u ntreated controls and 89% survival in the tolerant group (P < 0.0068). Hypotension caused an initial neutropenia in both groups. The circula ting PMN counts remained lower in the tolerant than in the controls ra ts for most of the low flow period. The number of circulating activate d PMNs in whole blood, as assessed by spontaneous nitroblue tetrazoliu m reduction, was lower in tolerant animals before and during most of t he hypotensive period, except immediately after bleeding when both gro ups have low circulating leukocyte counts. No detectable tumor necrosi s factor activity was observed in the plasma of either group. Adhesion of circulating PMNs to nylon fibers in vitro and the number of PMNs a dhering 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 PM N adhesion to endothelium with subsequent improvement of survival afte r hemorrhagic shock.