Impaired cytokine production by peripheral blood mononuclear cells in type 1 diabetic patients

Aims. - The objective of the present investigation was to study the production of IL-1, IL-6, IL-10, IFN gamma and TNF alpha in cultures of peripheral blood mononuclear cells (PBMC) taken from type 1 diabetic patients with inadequate metabolic control. Methods. - Seventeen type I diabetic patients and a gender- and age-matched group of 17 healthy individuals were studied. PBMC cultures were stimulated with phytohemagglutinin (PHA; 20 mu g/ml) and lipopolysaccharide (LPS; 10 mu g/ml), and enzyme immumoassay (Elisa) was used to measure IL-1, IL-6, IL-10, IFN gamma and TNF alpha in the cell-culture supernatants. Results. - IFN gamma levels in PHA-stimulated cultures were lower in the type I diabetics than in the non-diabetic controls (P < 0.0001) while, in contrast, IL-10 levels were increased in the PHA-stimulated culture supernatants of the diabetics compared with the controls (P < 0.0001). In addition, supernatant levels of the cytokines IL-1, IL-6 and TNFa released in the presence of LPS in the cell cultures from the diabetic patients were significantly lower than in the non-diabetic subjects (P < 0.0001, P < 0.0001 and P < 0.03, respectively). Conclusions. - The impaired production of IL-1, IL-6, TNF alpha and IFN gamma, and the increased production of IL-10, in PBMC cultures from type 1 diabetics with inadequate metabolic control compared with healthy subjects may be an indication of a deficiency in mononuclear cell activation and, consequently, a deficient immune cellular adaptive response that, in turn, may be the cause of the increased incidence of infections in people with type 1 diabetes. (C) 2007 Elsevier Masson SAS. All rights reserved.