Granulocyte/macrophage colony-stimulating factor increases wound-fluid interleukin 8 in normal subjects but does not accelerate wound healing.

Granulocyte/macrophage colony-stimulating factor (GM-CSF) is thought to play an important part under conditions of impaired wound healing. This is not confirmed and it is also unknown whether GM-CSF affects wound healing in healthy subjects. We conducted a randomized, double-blind, placebo-controlled pilot study in 10 healthy volunteers. Triplicate wounds (10 x 10 x 0.5 mm) on the right and left upper thigh were made by a razor blade and injected with GM-CSF or a solvent control. Four of the 10 volunteers were re-examined after 2 months by investigating the healing of a new set of triplicate wounds injected with solvent control alone (controls). Factors measured were wound healing time, wound-fluid cytokines by enzyme-linked immunosorbent assay, wound-fluid inflammatory cells and dermal thickness by ultrasonography. Intradermal injection with 20 micrograms GM-CSF per wound caused significantly higher wound-fluid GM-CSF and interleukin 8 (IL-8) levels than in controls, but did not affect the time needed for wound closure (mean 11 days in all groups), dermal thickness, wound-fluid inflammatory cells or other wound-fluid cytokines, e.g. vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). Transforming growth factor (TGF) beta 1 and beta 2, epidermal growth factor (EGF), and beta-fibroblast growth factor (beta-FGF) were not measurable in any wound fluid. The lack of efficacy of exogenously delivered GM-CSF on wound healing in healthy subjects is probably based on the failure of GM-CSF to induce 'wound-healing cytokines' like PDGF, FGF, TGF, EGF or VEGF. However, GM-CSF increases IL-8 release, which is a potent chemotactic cytokine, indicating that GM-CSF might be of therapeutic value under conditions of impaired chemotaxis.