The pattern of inflammatory/anti-inflammatory cytokines and chemokines in type 1 diabetic patients over time.

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.