JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, vol.16, no.2, pp.203-210, 2003 (SCI-Expanded)
Type 1 diabetes mellitus (DM) develops as a result of autoimmune destruction of the pancreatic beta-cells. The aim of this study was to explore possible associations between serum levels of cytokines, IL-1, IL-2, TNFalpha and INFgamma and metabolic parameters in children with type 1 DM and their non-diabetic siblings to determine whether these cytokines could be indicators of disordered immune regulation. The study population consisted of 41 children with type 1 DM, 32 non-diabetic siblings, and 28 healthy controls. Children with DM were divided into three subgroups: 1) newly diagnosed patients with diabetic ketoacidosis (ND + DKA), 2) newly diagnosed patients without DKA (ND - DKA), and 3) previously diagnosed patients (PD). The highest serum IL-1alpha level was found in the ND - DKA group, which was significant compared to both the ND + DKA (p <0.05) and the siblings (S) (p <0.005). IL-2 levels were similar among all groups. The highest TNFalpha level was observed in the ND + DKA group, which was significant against the ND - DKA (p <0.05), PD (p <0.001), S (p <0.05), and: control (C) (p <0.005) groups. TNFalpha concentration in the PD group was significantly lower than those of S (p <0.005) and C (p <0.001) groups. The ND - DKA group had the highest INFgamma and this was statistically significant when compared with the S (p <0.005) and C (p <0.05) groups. Both the newly diabetics and all diabetics as a group had statistically significantly higher INFgamma levels than both the S (p <0.01 for both) and C (p <0.05 for both) groups. In the diabetics as a whole group, TNFalpha showed correlations with INFgamma (r = 0.370, p <0.05). IL-1 showed correlation with TNFalpha (r = 0.368, p <0.05) INFgamma (r = 0.796, p <0.001) and IL-2 (r = 0.862, p <0.001) in the all diabetics group. IL-2 was correlated with TNFalpha (r = 0.320, p <0.05) and INFalpha (r = 0.754, p <0.01) in the all diabetics group. In conclusion, our results suggest that proinflammatory cytokines TNFalpha, INFgamma, IL1alpha and IL-2 may play important roles alone or in combination in the pathogenesis of type 1 diabetes mellitus.