Systemic inflammation may inhibit neutrophil (PMN) apoptosis and promote multiple organ dysfunction syndrome. We hypothesize that severe trauma causes dysregulation of PMN apoptosis.
Neutrophils were isolated from trauma patients (24–72 hours after injury; n = 16) and controls (healthy volunteers) and incubated for 18 hours. In separate experiments, control cells were treated ± the nuclear factor kappa beta (NFκβ) inhibitor pyrrolidinithiocarbamate then incubated with 25% patient or control plasma. Apoptosis was quantified by enzyme-linked immunosorbent assay for histone-associated DNA and annexin V fluorescence-activated cell sorter. NFκβ activation was determined by Western blot for phosphorylated Iκβ.
Apoptosis was inhibited in trauma patient PMN. Neutrophil apoptosis correlated with multiple organ dysfunction syndrome score, Acute Physiology and Chronic Health Evaluation II, and platelet count. Patient plasma inhibited apoptosis and induced phosphorylation of Iκβ in control cells. Inhibition of PMN apoptosis by patient plasma was blocked by pretreatment with pyrrolidinithiocarbamate.
NFκβ-dependent inhibition of neutrophil apoptosis occurs after trauma. Early inhibition of PMN apoptosis is dependent on the magnitude of injury.
From the Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts.
Address for reprints: Paul Bankey, MD, PhD, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655; email: Paul.Bankey@banyan.ummed.edu.
Submitted for publication September 24, 1999.
Accepted for publication January 6, 2000.
This research was supported by NIH grant 525753.
The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.
Presented at the 59th Annual Meeting of the American Association for the Surgery of Trauma, September 16–18, 1999, Boston, Massachusetts.