Interleukins and Eicosanoids: Pathogenetic Patterns of Diabetic Foot Ulcer

Abstract

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.

Role of Adaptation to Chronic Hypoxia in the Development of Dysimunic Disorders in Diabetic Foot Ulcer

“…Based on the above data, we could assume that in patients with infected chronic DFU, the reactivity of the humoral immune response is reduced, which, probably, in combination with weakened innate immunity [25] and a decrease in the absolute and relative number of CD19 + lymphocytes, contributes to the chronicity of tissue destruction. One of the protective mechanisms in this case may be cellular adaptation to O 2 deficiency, performed with the help of the hypoxia-inducible transcription factor-2 (HIF-2).…”