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.