Intracytoplasmic cytokine levels and neutrophil functions in early clinical stage of type 1 diabetes

Abstract

Studies indicate that both CD4(+) and CD8(+) T lymphocytes and their cytokines play a critical role in different clinical stages of type 1 diabetes (T1D). Disturbances of oxidative burst and phagocytic activities in neutrophils of diabetic patients compared to uncontrolled disease support the importance of neutrophil functions in the treatment and follow up of diabetic patients. This study is designed in order to investigate Th1 and Th2 cytokine profiles and neutrophil functions in early clinical stage of T1D. Patients diagnosed as T1D but not yet under insulin therapy (Group 1; n=15) and T1D patients with disease duration of <3 months (Group 2; n=20) were compared to healthy subjects (Group 3; n=15). All subjects with T1D were positive for islet cell antibody (ICA) and glutamic acid decarboxylase antibody (GADA), their fasting glucose levels were >126 mg/dl and A1(c) levels were >8. Intracytoplasmic interleukin (IL)-2, IL-10, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha levels of isolated CD4(+) and CD8(+) T cells, and neutrophil functions were determined by flow cytometry. Intracellular TNF-alpha level of CD4(+) T lymphocytes was significantly decreased in Group 1 compared to Group 2 and healthy subjects. In contrast, TNF-alpha in CD8(+) T lymphocytes was higher in Group 1 compared to Group 2. Increased TNF-alpha content of CD8(+) T lymphocytes was also obtained in Groups 1 and 2 compared to healthy subjects. Increased TNF-alpha secretion of CD8(+) T cells might reflect the role of CD8(+) T cells in beta cell destruction. Similar to cytokine content, phagocytic and oxidative burst activities in Group 1 were significantly lower compared to Group 2 and healthy subjects. Impaired neutrophil functions could be recovered by the treatment of the disease.