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

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.

Wound Fluid Diagnostics in Diabetic Foot Ulcers

“…Various modifications of this technique have been described with respect to used materials, patient preparation and time scales, as well as with respect to wound bed preparation (Trengove et al 1999;Trengove, Bielefeldt-Ohmann, and Stacey 2000;Yager et al 1996;Wysocki and Grinnell 1990;James et al 2000;Wallace and Stacey 1998;Chen et al 1997;Wysocki et al 1999;Gohel et al 2008). Even very comprehensive protocols aiming for standardisation have been proposed, including the prior fasting of patients for eight hours as well as grading their hydration status by drinking one litre of water while hanging down the leg (Trengove, Langton, and Stacey 1996).…”

“…To underline this thesis, Trengove et al were not able to detect significant changes within the levels of platelet-derived growth factor (PDGF), epidermal growth factor (EGF), basic fibroblast growth factor (bFGF) or transforming growth factor beta (TGF ) from healing and non-healing ulcers. However, in mitogenic assays in fibroblasts, wound fluid from healing ulcers was able to provoke a significantly enhanced proliferative response (Trengove, Bielefeldt-Ohmann, and Stacey 2000). Furthermore, additional growth factors have been implicated as playing an important role in wound healing, such as insulin-like growth factor (IGF) (Wagner et al 2003) or keratinocyte growth factor (KGF) (Gibbs et al 2000).…”

Short- and Long-Term Effects of IL-1 and TNF Antagonists on Periodontal Wound Healing

“…IL-1 can induce apoptosis (14) or antagonize apoptosis through activation of NF-B depending on the cell type (15). A small amount of IL-1 is necessary for host defense and wound healing (16), particularly in a challenging environment (17), whereas overproduction of IL-1 can hinder the early phase of wound healing (18,19). Two primary IL-1Rs (IL-1RI and IL-1RII) have been identified.…”

Computational Approach To Characterize Causative Factors and Molecular Indicators of Chronic Wound Inflammation

“…Yet, it has not been firmly established whether the expression of the same genes is altered in humans during disease, questioning the validity of such indicators. Any human study of chronic inflammatory diseases takes place well after the disease has already progressed and, thus, fails to provide insights into the factors triggering the chronic state (9,(18)(19)(20)(21)(22). Although chronic inflammation can be present in many pathological conditions, it is not causative to disease unless exacerbated by additional genetic and environmental factors (11).…”