Intracellular IFN-γProduction and IL-12 Serum Levels in Latent Autoimmune Diabetes of Adults (LADA) and in Type 2 Diabetes

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Abstract
Th1 cytokines, such as interleukin-2 (IL-2) and interferon-γ (IFN-γ), and Th1-inducing cytokines, such as IL-12, are involved in the pathogenesis of various organ-specific autoimmune diseases, including autoimmune diabetes. In this study, we investigated intracellular IFN-γ release by T lymphocytes and IL-12 serum levels in 48 type 2 and 36 latent autoimmune diabetes of adults (LADA) diabetics and 25 control subjects in an attempt to evaluate their role in the pathogenesis of these clinical entities. Ionomycin (ION) and phorbol-12-myristate-13-acetate (PMA)-activated peripheral blood mononuclear cells (PBMCs) were stained with anti-CD4-FITC or anti-CD8-FITC and anti-IFN-γ phycoerythrin (PE) monoclonal antibodies (mAbs) and analyzed by flow cytometry. IL-12 serum levels were determined by enzyme-linked immunosorbent assay (ELISA). In all study groups, IFN-γ content of CD4+ and CD8+ lymphocytes was significantly upregulated by stimulation. Furthermore, it was observed that CD4+ and CD8+ lymphocytes from type 2 diabetics produced significantly lower levels of IFN-γ compared with LADA patients and controls. However, the percentages of CD4+/IFN-γ+ and CD8+/IFN-γ+ cells from type 2 diabetics were significantly higher compared with controls. The flow cytometric picture of intracellular IFN-γ release in LADA patients did not differ from that observed in controls. However, IL-12 serum levels in type 2 and LADA diabetics were lower than in controls. Because Th1 cytokines have been associated with the pathogenesis of autoimmune diabetes, these results preclude Th1 involvement in the autoimmune phenomena observed in LADA patients. In contrast, the low IFN-γ levels observed in type 2 diabetics in combination with the low IL-12 serum levels might be a contributing factor in the frequently observed chronic complications in these patients.