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Circulating postinjury neutrophils are primed for the release of proinflammatory cytokines
G Zallen1, E E Moore, J L Johnson
1Department of Surgery, Denver Health Medical Center, Bonfils Blood Center, 80204, USA.
Background:
Postinjury neutrophil (PMN) priming identifies the injured patient at risk for the subsequent development of multiple organ failure (MOF). PMN priming has previously been shown to cause enhanced release of proteases and superoxide. PMNs, however, are a rich source of proinflammatory cytokines, such as interleukin (IL)-8 and tumor necrosis factor (TNF), which have 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 that postinjury PMNs are primed for increased stimulated release of the proinflammatory cytokines IL-8 and TNF but not the anti-inflammatory cytokine IL-1ra.
Methods:
Twelve trauma patients with a mean Injury Severity Score of 24 (+/-4.6) and 10 elective surgical patients were 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 obtained preoperatively, immediately postoperatively, and at 24 hours. The PMNs were stimulated with platelet-activating factor (200 nM)/N-formyl-methionyl-leucyl-phenylalanine (1 micromol/L) or lipopolysaccharide (100 ng/mL) incubated for 24 hours in RPMI-1640, and release of IL-8, TNF, and IL-1ra were measured.
Results:
Postinjury PMNs were primed for both platelet-activating factor/N-formyl-methionyl-leucyl-phenylalanine-stimulated and lipopolysaccharide-stimulated IL-8 and TNF release at 2 hours after injury (fourfold increase of IL-8 release and fivefold increase of TNF release), whereas elective surgical patients demonstrated no priming. In contrast, postinjury patients were not primed for increased release of the counterinflammatory cytokine IL-1ra, suggesting a specific postinjury up-regulation of IL-8 and TNF.
Conclusion:
After injury, PMNs are primed for proinflammatory cytokine release 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.
Insights
After injury, neutrophils are primed to release more inflammatory cytokines like IL-8 and TNF, but not anti-inflammatory IL-1ra. This heightened release may contribute to multiple organ failure (MOF) in trauma patients.
Area of Science:
- Immunology
- Trauma Research
- Cytokine Signaling
Background:
- Neutrophil (PMN) priming post-injury is linked to multiple organ failure (MOF) risk.
- Primed PMNs show enhanced release of proteases and superoxide.
- PMNs produce both pro-inflammatory (IL-8, TNF) and anti-inflammatory (IL-1ra) cytokines.
Purpose of the Study:
- To test the hypothesis that post-injury PMNs are primed for increased release of IL-8 and TNF.
- To determine if post-injury PMNs are also primed for increased release of IL-1ra.
- To investigate the specific cytokine release profile of neutrophils after trauma.
Main Methods:
- Studied 12 trauma patients and 10 elective surgical patients.
- Isolated PMNs at various time points post-injury or surgery.
- Stimulated PMNs and measured the release of IL-8, TNF, and IL-1ra.
Main Results:
- Post-injury PMNs showed significantly increased IL-8 and TNF release (4-5 fold) upon stimulation.
- No priming for increased IL-1ra release was observed in post-injury PMNs.
- Elective surgical patients did not exhibit PMN priming.
Conclusions:
- Neutrophils (PMNs) are primed after injury to release more pro-inflammatory cytokines (IL-8, TNF).
- This specific up-regulation of pro-inflammatory cytokines, not anti-inflammatory ones, may play a role in organ dysfunction.
- Augmented IL-8 and TNF release post-injury could contribute to the development of MOF.