T-Natural Killers and Interferon Gamma/Interleukin 4 in Augmentation of Infection in Foot Ulcer in Type 2 Diabetes

Abstract

Background The link between immune system and type 2 diabetes mellitus (T2DM) pathogenesis attracted attention to demonstrate the role of immune cells and their secreted cytokines in T2DM development and its subsequent foot complications. Objective To investigate the relation between T Natural killer cell (TNK) %, Interleukin 4 (IL4) and Interferon gamma (IFN-γ) and diabetic foot infection (DFI) development in patients with diabetic foot ulcer (DFU). Patients and Methods Ninety patients with diabetes were included in this work, divided as T2DM group (n=30), DFU group (n=30), and DFI group (n=30). TNK% was detected using flow cytometry. Serum IL4 and IFN-γ were measured by ELISA. Diabetes biochemical parameters were also analyzed. Results Significant decrease was detected in TNK% and IFN-γ in DFI group compared to other 2 groups ( P <0.001). Significant decrease was detected in serum levels of IL4 in DFI group compared to T2DM group ( P =0.006). IFN-γ/IL4 was significantly decreased in DFI compared to DFU group ( P =0.020). There was a significant correlation of TNK% with both IL4 and IFN-γ (r=0.385, P <0.001; r=0.534, P <0.001, respectively). Significant negative correlation of TNK% with HbA1c and LDL was revealed (r=−0.631, P <0.001; and r=−0.261, P =0.013, respectively), while a positive correlation was seen with HDL (r=0.287, P =0.006). A significant negative correlation of IL4 with HbA1c was found (r=−0.514, P <0.001;. As for IFN-γ, a significant negative correlation with HbA1c and LDL was detected (r=−0.369, P < 0.001; r=−0.229, P =0.030). TNK % and IFN-γ level showed negative correlations with disease duration/year (r=−0.546, P < 0.001; r=−0.338, P =0.001,respectively). Conclusion Decline in TNK frequency has essential role in T2DM pathogenesis and subsequent foot complications. Downregulation of TNK% and IFN-γ level have potential roles in predicting infection of diabetic ulcer and are correlated with disease duration.

Cigarette Smoking and Peripheral Vascular Disease are Associated with Increasing Risk of ESKAPE Pathogen Infection in Diabetic Foot Ulcers

“… 32 , 33 These findings seem to be consistent with the results of a previous study indicating that serum NKT% and IFN-γ were significantly decreased in patients with diabetic foot infection compared to patients with non-infected DFUs and diabetes only. 34 Furthermore, cigarette smoking can systemically decrease immune responses, leading to ESKAPE infection. 35 It has been shown that hyperglycemia affects the vasoconstriction response and platelet aggregation by inhibiting endothelial nitric oxide synthase activation and increasing reactive oxygen species, leading to atherothrombosis in the vessels and ultimately to peripheral vascular disease.…”

Bioinformatics analysis identifies TGF-β signaling pathway-associated molecular subtypes and gene signature in diabetic foot

“… 44 Compared to the type 2 diabetes mellitus group, a significant decrease in NKT and IFN-γ was observed in the diabetic foot infection group. 45 Based on the aforementioned findings, we posit that the TGF-β signaling pathway plays a significant role in the progression of DFU by modulating the infiltration of immune cells.…”

Analyzing Immune Cell Infiltration and Copper Metabolism in Diabetic Foot Ulcers

“… 26 A decrease in the frequency of NK cells plays a crucial role in the development of T2DM and its subsequent foot complications. 27 Chronic wounds, which are associated with dysregulated immune cells such as M1 macrophages, result from persistent inflammation and hinder the healing process of diabetic foot ulcers by disrupting the polarization of M2 macrophages. 28 The transition between classical and non-classical monocytes plays a crucial role in regulating inflammation and tissue repair during the healing of diabetic wounds.…”