Circulating postinjury neutrophils are primed for the release of proinflammatory cytokines

Background: Postinjury neutrophil (PMN) priming identifies the injured pati ent at risk for the subsequent development of multiple organ failure (MOP). PMN priming has previously been shown to cause enhanced release of proteas es and superoxide. PMNs, however, are a rich source of proinflammatory cyto kines, such as interleukin (IL)-8 and tumor necrosis factor (TNF), which ha ve been implicated in the development of MOF. PMNs also make IL-1ra, which is an anti-inflammatory cytokine that inhibits IL-1. It is our hypothesis t hat postinjury PMNs are primed for increased stimulated release of the proi nflammatory cytokines IL-8 and TNF but not the anti-inflammatory cytokine I L-1ra. Methods: Twelve trauma patients,with a mean Injury Severity Score of 24 (+/ -4.6) and 10 elective surgical patients mere studied. Postinjury PMNs were isolated from blood obtained at presentation (within 2 hours after injury) and 24 hours after trauma. PMNs from elective surgical patients were obtain ed preoperatively, immediately postoperatively, and at 24 hours. PMNs were stimulated with platelet-activating factor (200 nM)/N-formyl-methionyl-leuc yl-phenylalanine (1 mu mol/L) or lipopolysaccharide (100 ng/mL) incubated f or 24 hours in RPMI-1640, and release of IL-8, TNF, and IL-1ra mere measure d. Results: Postinjury PMNs were primed for both platelet-activating factor/N- formyl-methionyl-leucyl-phenylalanine- stimulated and lipopolysaccharide-st imulated IL-8 and TNF release at 2 hours after injury (fourfold increase of IL-8 release end fivefold increase of TNF release), whereas elective surgi cal patients demonstrated no priming. In contrast, postinjury patients were not primed for increased release of the counterinflammatory cytokine IL-1r a, suggesting a specific postinjury up-regulation of IL-8 and TNF. Conclusion: After injury, PHNs are primed for proinflammatory cytokine rele ase in addition to superoxide and elastase. This augmented release of IL-8 and TNF may be involved in the subsequent development of organ dysfunction and ultimately MOF.