DECREASED IN-VITRO AND IL-10 PRODUCTION BY PERIPHERAL-BLOOD IN FIRST DEGREE RELATIVES AT HIGH-RISK OF DIABETES TYPE-I

There is mounting evidence that the imbalance between Th-1 and Th-2 ly mphocyte subsets plays a key role in the development of autoimmune dia betes in NOD mice, but it is also possible in humans. The aim of the p resent study was the estimation of in vitro production of Th-1 (INF-ga mma, IL-2) and Th-2-derived (IL-4, IL-10) cytokines by peripheral bloo d in ICA and GADA positive first degree relatives of Type-I diabetes p atients, since they could represent primary events triggering an immun e-mediated islets destruction. The study was performed in 25 subjects at risk of insulin-dependent diabetes and 21 age- and sex-matched heal thy controls. Cytokine levels in supernatants of whole blood cultures with PHA (10 mu g/ml) were quantified by ELISA. We observed a lower co ncentration of IL-4 in culture supernatants in ICA and GADA positive r elatives as compared with the control group, both at 48 h and at 72 h of incubation. Similarly, in the prediabetic group, lower IL-10 levels at 48 and 72 h of culture were found. We did not observe statistical differences in in vitro production of IL-2 and INF-gamma by peripheral blood in high risk diabetes mellitus subjects and healthy controls. I n subjects at increased risk of Type-I diabetes, levels of IL-4 positi vely correlated with those of IL-10. There were negative correlations between IL-10 concentration after 48 h of incubation and levels of HbA (1)C. In conclusion our study has shown decreased IL-4 and IL-10 produ ction, but normal secretion of Th-1-derived cytokines by peripheral bl ood of prediabetic humans. This could suggest that the early stage of autoimmune process in Type-I diabetes in humans is associated with dec reased function of Th-2-cells rather than overactivation of Th-1 subse t in the peripheral blood.