The level of circulating cytokines and chemokines in the preclinical and early clinical stages of development of type 1A diabetes mellitus

Abstract

Aim: to study the level of circulating proinflammatory (IL-1α, IL-1β, IL-6, α-TNF, IFN-γ) and anti-inflammatory (IL-4, IL-10) cytokines and chemokines (IL-8, IL-16) in preclinical development of type 1A diabetes mellitus (T1DM) in children. Subjects and methods. An examination was made in 450 children who had normal blood glucose levels and a burdened history of positive or negative Langerhans islet autoantibodies (LIAA): IAA, GADA, and IA-2A over time until the clinical manifestations of DM1 emerged. The levels of the cytokines and chemokines were determined by ELISA and the titer of LIAA was by radioimmunoassay. Results. Long before T1DM was clinically diagnosed, most children with normal blood glucose levels and LIAA had elevated levels of the cytokines IL-1α, IL-6, and α-TNF and the chemoattractants IL-8 and IL-16 with lower IL-4 concentrations as compared with the similar indices in children without LIAA and controls. After the disease manifested, the magnitude of changes in the indices under study reduced in the majority of children with LIAA, which may suggest that the autoimmune process subsides after destruction of most β-cells. Conclusion. The elevated levels of IL-6, IL-16, α-TNF, and the chemokine IL-8 with the lower blood content of the cytokine IL-4 were long before the development of DM1 in children with normal blood glucose level in the presence of LIAA, which should be borne in mind while developing the immune mechanisms specifically directed against block, which participate by means of cytokines in β-cell destruction, as well as methods for preventing the development of T1DM in subjects with LIAA.

Keywords

• type 1a diabetes mellitus
• circulating cytokines
• β-cells
• pancreas