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 × 10 × 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 μg 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) β1 and β2, epidermal growth factor (EGF), and β‐fibroblast growth factor (β‐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.