We examined 40 patients with neuropathic (group 1, n=20) and neuroischemic (group 2, n=20) diabetic foot. Before surgical treatment, we studied the content of cytokines (TNF-α, IFN-γ, IL-1β, IL-6 and IL-10) and eicosanoids (LTB4 and PGE2) in the exudate of the ulcer discharge. Pathogenetic mechanisms of inflammation disorders in patients with neuropathic and neuroischemic forms of diabetic foot are different. The neuropathic form is characterized by an increase in the level of TNF-α and IL-6 in the wound exudate, inhibition of the IL-1β and IL-10 secretion, and the predominance of LTB4 in contrast to inhibition of PGE2 synthesis. At the same time, the formation of CD8+ is inhibited as well as the switching of the neutrophilic phase to the macrophage phase by maintaining the conditions for the differentiation of M1 macrophages. In the neuroischemic form, we revealed hyperproduction of IL-1β, IL-10, IFN-γ, CD4+ with inhibition of IL-6 secretion and eicosanoids imbalance (PGE2 prevail over LTB4). This disrupts the differentiation of M2 macrophages. All identified disorders may be due to the persistence of various neutrophil phenotypes in the wound.

The article presents a comparative assessment of the levels of cytokines that regulate the differentiation of various macrophage phenotypes, as well as immunological responses in patients with diabetes. We examined and treated 245 patients who were allocated to two groups. The first group comprised neuropathic patients (comparison subgroup 1A without DFU, n=30 and subgroup 1B with DFU, n=80). The second group included patients with neuroischemic type 2 diabetes (comparison subgroup 2A without DFU, n=35 and subgroup 2B with DFU, n=100). As an indicator of hyperglycemia, the glycated hemoglobin level (HbA1c) was used, which was determined on the DCA 2000 device by the method of latex immunoagglutination inhibition using the “Hemoglobin A1c Reagent kit”. The concentration of cytokines TNF-α, IFN-γ, IL-6, and OPG in blood serum was determined on the first day of hospitalization before surgery using enzyme immunoassay test systems (OOO “Cytokine”, St. Petersburg) in accordance with the manufacturer's instructions. An imbalance of cytokines was revealed, indicating a shift in immunomodulatory responses, aggravation of metabolic and vascular disorders in tissues, accompanied by an inadequate course of the inflammatory and reparative process and the formation of a diabetic foot ulcer.