Neutrophils are primed for cytotoxicity and resist apoptosis in injured patients at risk for multiple organ failure

Background. Postinjury multiple organ failure (MOF) is the result of a dysr egulated systemic inflammatory response in which primed neutrophils (PMNs) are sequestered in tissues, vulnerable to activation through secondary insu lts. Apoptosis is critical to the normal clearance of these sequestered PMN s. Conversely, dysfunctional apoptosis prolongs the PMN functional life spa n, potentially exacerbating PMN-mediated tissue injury and the development of MOF. We hypothesized that severe trauma, in addition to priming PMNs, pr ovokes dysfunctional PMN apoptosis. Methods. Neutrophils were harvested daily from 12 severely injured patients at high risk for MOF; cultured for 24 hours, and assessed for apoptosis wi th use of acridine orange-ethidium bromide staining and fluorescence micros copy. Priming for elastase release was measured in freshly isolated patient PMNs. Plasma from patients was assessed for its ability to delay apoptosis of normal PMNs. Results. Four patients (33%) had MOF: Neutrophil apoptosis was profoundly d elayed in severely injured patients throughout the 5-day study period. Prim ing for elastase release was augmented concomitantly. Patients' plasma dela yed apoptosis of normal PMNs. Conclusion. rn patients at high risk for postinjury MOF, PMNs are not only primed for cytotoxicity but also resist apoptosis. The dysfunctional apopto sis is attributed, at least in part, to a plasma-borne mediator. The net ef fect may facilitate hyperinflammatory organ injury.