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 Th₁ and Th₂ lymphocyte subsets plays a key role in the development of autoimmune diabetes in NOD mice, but it is also possible in humans. The aim of the present study was the estimation of in vitro production of Th₁ (INF-γ, IL-2) and Th₂-derived (IL-4, IL-10) cytokines by peripheral blood in ICA and GADA positive first degree relatives of Type-I diabetes patients, since they could represent primary events triggering an immune-mediated islets destruction. The study was performed in 25 subjects at risk of insulin-dependent diabetes and 21 age- and sex-matched healthy controls. Cytokine levels in supernatants of whole blood cultures with PHA (10 µg/ml) were quantified by ELISA. We observed a lower concentration of IL-4 in culture supernatants in ICA and GADA positive relatives as compared with the contol 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-γ by peripheral blood in high risk diabetes mellitus subjects and healthy controls. In subjects at increased risk of Type-I diabetes, levels of IL-4 positively correlated with those of IL-10. There were negative correlations between IL-10 concentration after 48 h of incubation and levels of HbA₁C. In conclusion our study has shown decreased IL-4 and IL-10 production, but normal secretion of Th₁-derived cytokines by peripheral blood of prediabetic humans. This could suggest that the early stage of autoimmune process in Type-I diabetes in humans is associated with decreased function of Th₂-cells rather than overactivation of Th₁ subset in the peripheral blood.

Type-I Diabetes - Th₁ Lymphocytes - Pathogenesis