Cytokine expression in unstimulated PBMC of children with type 1 diabetes and subjects positive for diabetes-associated autoantibodies

The aim of this study was to evaluate possible changes in the circulating l evels of interferon (IFN)-gamma, interleukin (IL)-4 and transforming growth factor (TGF)-beta in association with the autoimmune process leading to ty pe 1 diabetes, Expression levels of mRNAs specific for each cytokine were d etermined in peripheral blood mononuclear cells (PBMC) by a multiplex rever se transcription-polymerase chain reaction (RT-PCR) followed by hybridizati on reactions with lanthanide-labelled probes and detection by time-resolved fluorometry. Newly diagnosed diabetic children had lower levels of IFN-gam ma, IL-4 and TGF-beta1 signals compared to their age- and sex-matched contr ols (P < 0.02, P < 0.005 and P < 0.005, respectively) and also the autoanti body-positive subjects had significantly lower levels of IL-4 and TGF-<beta >1 in comparison with their matched controls (P = 0.0013 and P = 0.012). No significant differences were observed when comparing matched pairs of diab etic children and autoantibody-positive subjects. Our results suggest a sys temic bias towards reduced production of T-helper cell type 2 cytokines (IL -4 and TGF-beta1) during the autoimmune process, but there was also a reduc ed level of IFN-gamma expression in the periphery at the onset of clinical diabetes.