Use of a non-specific immunomodulation therapy as a therapeutic vasculogenesis strategy in no-option critical limb ischemia patients

Background/aimsInflammatory mediators contribute to the impairment of vasculogenesis by reducing endothelial progenitor cells (EPCs) mobilization in atherosclerotic vasculopathy.We tested the hypothesis that administration of an oxygen/ozone mixture (IMT) might counteract this pathophysiological mechanism and enhance limb tissue perfusion in patients with critical limb ischemia (CLI).MethodsRandomized patients with rest pain or ischemic ulcers and transcutaneous oxygen tension (TcPO₂) <40 mmHg and/or toe pressure <50 mmHg received placebo (n = 74) or a non-specific immunomodulation therapy (IMT) (n = 77), autologous blood exposed to oxygen/ozone gas mixture by intragluteal injection, on day 1, 2, 7, and once a week thereafter for at least 22 weeks. Patients were evaluated for changes in TcPO₂, levels of circulating EPCs (CD34/KDR-positive cells) and inflammation (tumor necrosis factor-α—TNF-α).ResultsTcPO₂ and CD34/CD133-positive cells increased at 22 weeks in IMT group (P < 0.01) whereas no changes were observed in placebo group. TNF-α levels decreased at 6 months in IMT group (P < 0.001) whereas no changes were observed in placebo group. There was a strong positive correlation between CD34/KDR-positive cells and TcPO₂ (r = 0.56, P < 0.01). Moreover, there was an inverse correlation between CD34/KDR-positive cells and TNF-α (r = ?0.51, P < 0.01).ConclusionsIntramuscular injection of IMT may improve wound healing and limb salvage in patients with CLI.