Immunomarker profiling in human chronic wound swabs reveals IL-1 beta/IL-1RA and CXCL8/CXCL10 ratios as potential biomarkers for wound healing, infection status and regenerative stage.

Background: Chronic wounds, such as diabetic foot ulcers, venous leg ulcers, and post-surgical wound healing disorders pose a significant challenge due to prolonged healing, risk of infection, and impaired quality of life. Persistent inflammation and impaired tissue remodeling are common in these wounds. Traditional diagnostic methods, including visual inspection and microbiological cultures, offer limited insight into the wound micro-environment. Immunomarker profiling could provide a deeper understanding of the molecular mechanisms underpinning wound healing, offering potential biomarkers for infection status and healing progression.

Methods: This observational, multi-center cohort study, part of the 'Wound-BIOME' project, analyzed 110 swab samples from patients with acute and chronic wounds using multiplex immunoassays. Clinical parameters such as wound type, healing status, regeneration stage, and microbial burden were recorded. Total protein concentration was assessed, and 35 key immunomarkers, including cytokines (e.g. IL- 1α, IL- 1β), chemokines (CCL2, CXCL8, CXCL10), growth factors (FGF- 2, VEGF) and matrix metalloproteinases (MMP- 7, MMP- 9, MMP- 13), were quantified. Statistical analyses were performed to correlate immunomarker levels with clinical outcomes.

Results: Pro-inflammatory markers, such as IL- 1β, IL- 18 and chemokines like CCL2 and CXCL8, were significantly elevated in non-healing and infected wounds compared to healing wounds. The study identified two new immunomarker ratios - IL- 1β/IL- 1RA and CXCL8/CXCL10 - as potential predictors of wound healing status. The IL- 1β/IL- 1RA ratio showed the highest accuracy for distinguishing healing from non-healing wounds (AUC = 0.6837), while the CXCL8/CXCL10 ratio was most effective in identifying infection (AUC = 0.7669).

Conclusions: Immunomarker profiling via wound swabbing offers valuable insights into the wound healing process. Elevated levels of pro-inflammatory cytokines and MMPs are associated with chronic inflammation and impaired healing. The IL- 1β/IL- 1RA and CXCL8/CXCL10 ratios emerge as promising biomarkers to distinguish between infection and inflammation, with potential in targeted wound care. Further studies are needed to validate these findings and implement them in clinical practice.