Serum IL-8 and CXCR2 Gene Expression as Indicators of Bone Fracture Healing Progression and Impairment

Abstract

Background: In bone fracture, IL-8 is an inflammatory chemokine produced at the injury site, signaling for the rapid recruitment of immune cells. CXCR2 is the receptor on these cells, primarily neutrophils, that binds to IL-8, orchestrating their essential migration to the fracture to clear debris and initiate the healing process.

Aim: This study investigated the potential of IL-8 and its receptor, CXCR2, as predictive markers for fracture healing outcomes. Serum levels of IL-8 were measured, and CXCR2 gene expression was quantified.

Materials and methods: Serum levels of MCP-1 and IL-8 were measured using enzyme-linked immunosorbent assays, while the expression of CCR2 and CXCR2 genes was quantified by real-time PCR. Receiver operating characteristic curve analysis was performed to evaluate the diagnostic accuracy of these biomarkers

Results: The results revealed significantly elevated serum IL-8 levels in both patients with normal fracture healing and those with delayed healing compared to healthy controls. Notably, IL-8 levels were significantly higher in the delayed healing group compared to the normal healing group. Receiver operating characteristic curve analysis demonstrated excellent diagnostic accuracy for IL-8, with effectively distinguishing normal healing patients from controls and delayed healing patients from controls. Consistent with the elevated chemokine levels, gene expression analysis revealed significantly upregulated CXCR2 in both normal healing and delayed healing patients compared to controls. The expression of CXCR2 remained persistently elevated across different healing stages, with the highest levels observed in the delayed healing and maturation stages. Receiver operating characteristic (ROC) analysis demonstrated that CXCR2 gene expression could perfectly distinguish normal healing and delayed healing patients from healthy controls. Mechanistically, IL-8 and CXCR2 mediate neutrophil chemotaxis and activation, which are essential for clearing debris and initiating tissue repair. However, excessive or prolonged CXCR2 signaling can contribute to chronic inflammation and impair bone regeneration. The exceptional diagnostic accuracy of these biomarkers underscores their potential clinical utility. Measuring serum IL-8 levels and quantifying CXCR2 gene expression could aid in the early identification of patients at risk of delayed healing, enabling timely implementation of targeted interventions. Furthermore, the IL-8/CXCR2 axis represents a promising therapeutic target, and modulating this pathway may offer novel strategies to optimize fracture repair, particularly in high-risk populations.

Conclusion:This study demonstrates the significant potential of IL-8 and CXCR2 as prognostic biomarkers for fracture healing outcomes. Their elevated levels, particularly in delayed healing patients, underscore their involvement in pathogenesis of impaired bone regeneration. Integrating the assessment of these biomarkers into clinical practice may enhance risk stratification and guide targeted therapeutic interventions to improve fracture healing rates and patient outcomes.