Inhibition of neutrophil apoptosis after severe trauma is NF kappa B dependent

Background: Systemic inflammation may inhibit neutrophil (PMN) apoptosis an d promote multiple organ dysfunction syndrome. We hypothesize that severe t rauma causes dysregulation of PMN apoptosis. Methods: Neutrophils were isolated from trauma patients (24-72 hours after injury; n = 16) and controls (healthy volunteers) and incubated for 18 hour s. In separate experiments, control cells were treated +/- the nuclear fact or kappa beta (NF kappa beta) inhibitor pyrrolidinithiocarbamate then incub ated with 25% patient or control plasma, Apoptosis was quantified by enzyme -linked immunosorbent assay for histone-associated DNA and annexin V fluore scence-activated cell sorter. NF kappa beta activation was determined by We stern blot for phosphorylated I kappa beta. Results: Apoptosis was inhibited in trauma patient PMN. Neutrophil apoptosi s correlated with multiple organ dysfunction syndrome score, Acute Physiolo gy and Chronic Health Evaluation II, and platelet count. Patient plasma inh ibited apoptosis and induced phosphorylation of I kappa beta in control cel ls. Inhibition of PMN apoptosis by patient plasma was blocked by pretreatme nt with pyrrolidinithiocarbamate. Conclusion: NF kappa beta-dependent inhibition of neutrophil apoptosis occu rs after trauma. Early inhibition of PMN apoptosis is dependent on the magn itude of injury.