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Kim, Bong-Sung; Breuer, Benjamin; Arnke, Kevin; Ruhl, Tim; Hofer, Tanja; Simons, David; Knobe, Matthias; Ganse, Bergita; Guidi, Marco; Beier, Justus P.; Fuchs, Paul C.; Pallua, Norbert; Bernhagen, Jürgen; Grieb, Gerrit (2020): The effect of the macrophage migration inhibitory factor (MIF) on excisional wound healing in vivo. In: Journal of Plastic Surgery and Hand Surgery, Vol. 54, No. 3: pp. 137-144
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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 alpha (TNF alpha) 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, TNF alpha 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.