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

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 improveme nts 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 ha d changed from a nonhealing to a healing phase. These samples were used to assess cytokine and growth factor levels, and mitogenic activity in these n onhealing and healing chronic wounds. The proinflammatory cytokines interle ukin-1, interleukin-6 and tumor necrosis factor-alpha were found to be pres ent in significantly higher concentrations in wound fluid from nonhealing c ompared to healing leg ulcers. There were detectable levels but, no signifi cant change in the levels of platelet derived growth factor, epidermal grow th factor, basic fibroblast growth factor or transforming growth factor-bet a as ulcers healed. Wound fluid was added to fibroblasts in vitro to assess mitogenic activity. There was a significantly greater proliferative respon se to healing wound fluid samples compared to nonhealing samples. These res ults suggest that healing may be impaired by inflammatory mediators rather than inhibited by a deficiency of growth factors in these chronic wounds.