*Article* **IL10 Alters Peri-Collateral Macrophage Polarization and Hind-Limb Reperfusion in Mice after Femoral Artery Ligation**

**Alexander M. Götze 1,\*, Christian Schubert 2, Georg Jung 3, Oliver Dörr 4, Christoph Liebetrau 5, Christian W. Hamm 5, Thomas Schmitz-Rixen 3, Christian Troidl 4,**† **and Kerstin Troidl 2,3,**†


Received: 31 March 2020; Accepted: 15 April 2020; Published: 17 April 2020

**Abstract:** Arteriogenesis is a process by which a pre-existing arterioarterial anastomosis develops into a functional collateral network following an arterial occlusion. Alternatively activated macrophages polarized by IL10 have been described to promote collateral growth. This study investigates the e ffect of di fferent levels of IL10 on hind-limb reperfusion and the distribution of perivascular macrophage activation types in mice after femoral artery ligation (FAL). IL10 and anti-IL10 were administered before FAL and the arteriogenic response was measured by Laser-Doppler-Imaging perioperatively, after 3, 7, and 14 d. Reperfusion recovery was accelerated when treated with IL10 and impaired with anti-IL10. Furthermore, symptoms of ischemia on ligated hind-limbs had the highest incidence after application of anti-IL10. Perivascular macrophages were immunohistologically phenotyped using CD163 and CD68 in adductor muscle segments. The proportion of alternatively activated macrophages (CD163+/CD68+) in relation to classically activated macrophages (CD163−/CD68<sup>+</sup>) observed was the highest when treated with IL10 and suppressed with anti-IL10. This study underlines the proarteriogenic response with increased levels of IL10 and demonstrates an in-vivo alteration of macrophage activation types in the perivascular bed of growing collaterals.

**Keywords:** arteriogenesis; collateral artery; macrophages; macrophage polarization; M2 macrophages; IL10
