Induction of Interferon-γ and IL-4 Production by Mitogen and Specific Antigens in Peripheral Blood Lymphocytes of Type 1 Diabetes Patients

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Abstract
A functional imbalance in cytokine production resulting in dominance of Thl over Th2 type response has been suggested to play a critical role in the pathogenesis of type 1 diabetes. In this study the cellular responses to pokeweed mitogen and a panel of specific antigens were analysed by measuring the production of IFN-γ and IL-4 cytokines at the levels of mRNA expression (expression index=antigen/medium) and protein secretion in culture supernatants. Two enterovirus preparates were included due to the suggested significance of these viruses in the aetiology of type 1 diabetes. The study included 22 children with newly-diagnosed type 1 diabetes, 15 children with longer duration of disease and 20 healthy children. Comparisons were made between age- and sex-matched groups. Newly diagnosed diabetic patients had significantly higher IFN-γ mRNA expression index (p<0.02) but also higher IL-4 mRNA expression index (p<0.05) in tetanus toxoid stimulated peripheral blood mononuclear cells compared to healthy controls. Also the diabetic patients studied 3-72 months after the diagnosis of type 1 diabetes showed a tendency to higher IFN-γ mRNA expression index compared to controls (0.05<p<0.1). Enhanced mitogen-stimulated IFN-γ mRNA expression index was observed in children with newly-diagnosed type 1 diabetes when compared to subjects with longer duration of diabetes (p<0.05). No significant differences were observed in IFN-γ produced into the culture supernatants. In conclusion, imbalance in both IFN-γ and IL-4 mRNA levels was demonstrated between diabetic patients and healthy subjects