Mitogenic activity and cytokine levels in non‐healing and healing chronic leg ulcers

TLDR

The cause of impaired healing in chronic leg ulcers is unknown, and adding growth factors has not markedly improved outcomes. This study aimed to compare cytokine, growth factor, and mitogenic activity in wound fluid from chronic venous leg ulcers that transitioned from nonhealing to healing. Wound fluid was collected from such ulcers, analyzed for cytokine and growth factor concentrations, and applied to fibroblasts in vitro to assess mitogenic responses. Nonhealing ulcers had markedly higher IL‑1, IL‑6, and TNF‑α, while growth factor levels were unchanged, and healing fluid stimulated greater fibroblast proliferation, indicating inflammation rather than growth factor deficiency impairs healing.

Abstract

The cause of impaired healing in chronic leg ulcers is not known. However, recent attempts to modify the healing process have focused on adding growth factors to stimulate healing and have failed to produce dramatic improvements in healing. This study used a unique model of chronic wound healing in humans to obtain wound fluid samples from chronic venous leg ulcers that had changed from a nonhealing to a healing phase. These samples were used to assess cytokine and growth factor levels, and mitogenic activity in these nonhealing and healing chronic wounds. The pro-inflammatory cytokines interleukin-1, interleukin-6 and tumor necrosis factor-alphawere found to be present in significantly higher concentrations in wound fluid from nonhealing compared to healing leg ulcers. There were detectable levels but, no significant change in the levels of platelet derived growth factor, epidermal growth factor, basic fibroblast growth factor or transforming growth factor-betaas ulcers healed. Wound fluid was added to fibroblasts in vitro to assess mitogenic activity. There was a significantly greater proliferative response to healing wound fluid samples compared to nonhealing samples. These results suggest that healing may be impaired by inflammatory mediators rather than inhibited by a deficiency of growth factors in these chronic wounds.