Aims: To evaluate the profile of pro- and anti-inflammatory cytokines in type 1 diabetes mellitus (T1DM) and the way they are connected in co-regulated networks and determine whether disease duration influences their pattern.
Methods: Plasma levels of 20 cytokines and soluble CD40 (sCD40) from 44 uncomplicated patients and 22 healthy controls (HCs) were measured using enzyme-linked immunosorbent assay (ELISA) and protein array technology.
Results: Patients showed significantly higher levels of sCD40, IL-1a, IL-2, IL-4, IL-5, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1a, MIP-1b, regulated on activation normal T cell expressed and secreted (RANTES), matrix metalloproteinase (MMP)-9, and a trend to higher IL-6 than did HCs. RANTES and sCD40 discriminated significantly between diabetics and HCs. In patients with disease duration >6 months, cytokines were organized in two clusters mainly regulated by Th17 and Th1/Th2 cells respectively, while in those with disease duration <or=6 months a set of Th1-cytokines was separated apart from the second cluster. Monocyte chemotactic protein (MCP)-1 was revealed as the most discriminant factor between patients with disease duration of more than and less than 6 months.
Conclusions: A parallel elevation of both inflammatory and anti-inflammatory cytokines was observed in patients compared with HCs. In T1DM patients with disease duration <or=6 months, Th1-cytokines were organized on a separate cluster, suggesting a possible role of Th1 cells in the progress of beta-cell destruction during the first period of the disease.