The effect of the macrophage migration inhibitory factor (MIF) on excisional wound healing in vivo

Abstract

Background: The macrophage migration inhibitory factor (MIF) has been determined as a cytokine exerting a multitude of effects in inflammation and angiogenesis. Earlier studies have indicated that MIF may also be involved in wound healing and flap surgery. Methods: We investigated the effect of MIF in an excisional wound model in wildtype, Mif^-/- and recombinant MIF treated mice. Wound closure rates as well as the macrophage marker Mac-3, the pro-inflammatory cytokine tumor necrosis factor α (TNFα) and the pro-angiogenic factor von Willebrand factor (vWF) were measured. Finally, we used a flap model in Mif^-/- and WT mice with an established perfusion gradient to identify MIF’s contribution in flap perfusion. Results: In the excision wound model, we found reduced wound healing after MIF injection, whereas Mif deletion improved wound healing. Furthermore, a reduced expression of Mac-3, TNFα and vWF in Mif^-/- mice was seen when compared to WT mice. In the flap model, Mif^-/- knockout mice showed mitigated flap perfusion with lower hemoglobin content and oxygen saturation as measured by O₂C measurements when compared to WT mice. Conclusions: Our data suggest an inhibiting effect of MIF in wound healing with increased inflammation and perfusion. In flaps, by contrast, MIF may contribute to flap vascularization.

Keywords:

• MIF
• wound healing
• flap model
• excisional wound
• perfusion
• hypoxia
• macrophages

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

Bong-Sung Kim and Kevin Arnke were supported by the Deutsche Forschungsgemeinschaft (DFG) [KI1973/2-1]. Jürgen Bernhagen was supported by DFG grants [SFB 1123/A03, BE1977/7-1, BE1977/11-1].