Modulation of Interleukin-8-Mediated Neutrophil Migration Following Major Lower-Limb Fracture and Operative Stabilization

Abstract

Background and Purpose:

Neutrophil-mediated tissue injury is the hallmark of acute respiratory distress syndrome (ARDS) following trauma. However, neutrophil migration into tissues is a critical, but poorly understood step. The authors investigated the changes in interleukin-(IL-)8-mediated neutrophil migration and associated receptor expression of the IL-8 receptor CXCR1, platelet endothelial cell adhesion molecule-1 (PECAM-1) and the integrins CD18/CD11b, in patients with isolated major lower-limb fractures undergoing fracture surgery.

Patients and Methods:

In this observational study, 18 patients with isolated major lower-limb fractures (pelvis, femur, tibia) with no serious preexisting disease were studied prospectively. Twelve underwent reamed nailing and six were treated with an external fixator. Eleven normal volunteers were used as controls. Blood samples were obtained within 4 ± 2 h of injury, at 24 h, day 3 and day 5. Neutrophils migration was assessed by an in vitro IL-8 assay and receptor expression by FACScan. Plasma IL-6 and its soluble receptor (sIL-6R) were measured by enzyme-linked immunosorbent assay (ELISA). Clinical progress was monitored over a 5-day period.

Results:

Similar systemic responses to injury were demonstrated by elevated IL-6 (p < 0.01) and sIL-6R (p < 0.01) levels on admission in both groups of patients. Significantly greater numbers of patient neutrophils migrated on admission as compared with normal volunteers (p < 0.05); this was associated with a significant increase in CXCR1 (p < 0.05) and downregulation of PECAM-1 (p < 0.05). A further increase was observed following reamed nailing (p < 0.05) but not with external fixation. On day 5, migration was subnormal in those patients managed with external fixation (p < 0.01).

Conclusion:

Following major lower-limb fracture, neutrophils are primed for increased IL-8-mediated migration. Stabilization by reamed nailing further elevates this response and could increase the risk of ARDS.