Abstract
Background: This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. Methods: A total of 121 patients with T2DM (79 without diabetic foot syndrome (DFS) and 42 patients with DFS) were included. Cluster of Differentiation 14 (CD14+) monocytes were isolated from patients’ blood and stimulated by interferon-γ (IFN-γ) and interleukin-4 (IL-4) for induction of pro- and anti-inflammatory monocyte activation, respectively. The concentrations of TNF-α and CCL18 in the culture medium were measured using ELISA on day 1 and day 6 after cell stimulation. Results: We found a correlation between glycated hemoglobin (HbA1c) and stimulated secretion levels of TNF-α (r = 0.726, p = 0.027) and CCL18 (r = –0.949, p = 0.051) in patients with DFS. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS (p < 0.05). However, no stimulation of anti-inflammatory activation was detected in patients with DFS lasting more than 6 months (p = 0.033). Conclusions: Our study showed an increase in pro-inflammatory secretion and a decrease in anti-inflammatory secretion by monocytes isolated from blood of patients with T2DM depending on HbA1c levels and duration of the inflammatory process. These findings allow us to assume that monocytes isolated from T2DM patients are characterized by a biased ability to respond towards pro-inflammatory stimulation, contributing to the chronic wound process.
Highlights
Diabetes mellitus (DM) is an endocrine disease characterized by chronic hyperglycemia
In the setting of hyperglycemia, atherosclerosis progresses as a result of oxidative modification of low density lipoproteins (LDL) followed by enhanced absorption by monocytes, which are transformed into foam cells involved in the pre-atherogenic lipid infiltration of the vascular wall [7,8]
Following IFN-γ stimulation we found a 1.31-fold increase in the pro-inflammatory response (p < 0.001)
Summary
Diabetes mellitus (DM) is an endocrine disease characterized by chronic hyperglycemia. Signs of local and systemic nonspecific inflammatory processes in atherosclerosis emerge at initial stages of lesion in the artery wall [11,12] Blood cells such as monocytes play a key role in the process of atherosclerotic inflammation. This study involves the investigation of spontaneous and induced secretion of the pro-inflammatory cytokine tumor necrosis factor-α (TNF-α) and the anti-inflammatory chemokine C-C motif chemokine ligand 18 (CCL18) by monocytes isolated from blood of patients with long-term type 2 diabetes mellitus (T2DM), both with or without foot ulcers. There was an increase of pro- and anti-inflammatory activation of monocytes in all patients with different durations of DFS (p < 0.05)
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